Alzheimer Type Research Articles

Baseline characterization of the ARMADA (Assessing Reliable Measurement in Alzheimer's Disease) study cohorts.

The National Institutes of Health (NIH) Toolbox (NIHTB) provides computerized measures of cognition, emotion, sensation, and motor abilities across the lifespan. The ARMADA (Assessing Reliable Measurement in Alzheimer's Disease and Cognitive Aging) study validated the NIHTB in individuals across the cognitive aging spectrum. This article reports the characteristics of our sample of participants. Participants were recruited across nine sites and classified clinically as cognitively normal (NC), with mild cognitive impairment (MCI), or with dementia of the Alzheimer's type (DAT.) They completed the NIHTB at multiple time points and many had at least one Alzheimer's biomarker previously obtained. Groups differed with respect to dementia severity levels, as anticipated, but were well-matched across many demographic characteristics. The ARMADA study demographics and baseline characteristics provide a suitable sample for validating the NIHTB across the cognitive aging spectrum. Other enriched samples (African American participants, Spanish NIHTB, 85+ years of age) will be reported elsewhere. There is a need for assessments that can detect the early stages of cognitive decline in older adults. The ARMADA (Assessing Reliable Measurement in Alzheimer's Disease and Cognitive Aging) study will validate the National Institutes of Health (NIH) Toolbox across the aging spectrum, including mild cognitive impairment (MCI) and dementia of the Alzheimer's type (DAT). Here we report the characteristics of participants. Groups were well-matched across most demographic characteristics, and clinical characteristics differed as expected. ARMADA study cohorts reflect their respective clinical syndromes for validating the NIH Toolbox.

Sentence repetition span in primary progressive aphasia and Alzheimer's disease: Insights from preliminary results

Primary Progressive Aphasia (PPA) is a neurocognitive disorder ascribed to cortical atrophy impacting language abilities. It is widely classified into three main variants, logopenic PPA (lvPPA), the semantic variant of PPA (svPPA), and the non-fluent PPA (nfvPPA), showing different impairment patterns across variants. However, in the early phases of PPA, it is not always easy to dissociate different PPA variants and distinguish PPA from other neurodegenerative disorders. One characteristic language symptom that seems to be a distinguishing factor of PPA, especially the logopenic variant, is impaired sentence repetition. Nonetheless, studies examining sentence repetition in PPA, and Alzheimer's disease (AD) more broadly, have resulted in mixed findings. To better understand the working memory-intensive nature of sentence repetition deficits, we designed a sentence repetition span task. We seek to understand (i) whether three diagnostic groups (lvPPA, svPPA, and AD) encounter greater sentence repetition difficulties than the controls, and (ii) whether using a span task design, in which the number of content words increases as the span length increases, would help dissociate PPA variants from AD type dementia. In this study, we administered a sentence repetition span task to four groups of French-speaking individuals with lvPPA (n = 14), svPPA (n = 5), and with AD (n = 13), and their age-matched healthy controls (n = 61). The results showed that all three diagnostic groups (lvPPA, svPPA, and AD) performed equally poorly compared to the controls on the repetition span task virtually in all measures (i.e., sentence span, the number of content words, and the number of omission and substitution errors). One intriguing finding was that the lvPPA group produced an exalted number of phonological errors during repeating sentences, while this type of error was somewhat moderate in the svPPA group and only minimal in the AD group. We conclude that the sentence repetition difficulty in PPA and AD should be modulated by working memory capacity, as our participants undoubtedly demonstrated greater difficulty as the span length increased. However, we note that working memory-intensive sentence repetition deficits based on the number of content words might not reveal critical diagnostic differences between the neurodegenerative groups.

The common genes involved in the pathogenesis of Alzheimer's disease and type 2 diabetes and their implication for drug repositioning

BackgroundThe prevalences of Alzheimer's disease (AD) and type 2 diabetes (T2D) continuously increase with the aging of world population. Clinical and epidemiological studies indicate that T2D is an important risk factor for AD. However, the mechanisms underlying the linkage of the two disorders are still not fully elucidated. The aim of this study is to explore the molecular mechanisms of their comorbidity and potential drug targets for AD treatment. MethodsWe first compiled comprehensive lists of genes associated with AD and T2D, respectively. Then, we investigated the signatures of the shared genes and screened for interactions between the hub genes. Subsequently, we used Autodock Vina to perform molecular docking to predict new drug candidates. Lastly, structure and dynamics of docking results were examined by molecular dynamics simulation to verify drug reliability. ResultsWe obtained 917 AD-associated genes, 631 T2D-associated genes and 175 shared genes between the two disorders for subsequent analyses. Functional analysis revealed that metabolic process, lipid and atherosclerosis, AMPK signaling pathway, insulin resistance, chemokines and cytokines were enriched in the shared genes. In addition, 50 central hub genes were identified, including IL6, TNF, INS, IL1B, AKT1, VEGFA, IL10, TP53, PTGS2, TLR4, and others. Finally, we predicted new drug candidates (verdoheme and stannsoporfin) that could be potentially used for AD treatment. ConclusionsOur study confirmed that there are important shared genes and pathways between AD and T2D, which may provide clues to reveal the molecular mechanism underlying the pathophysiology of the two diseases and help us to discover novel drug candidates for the treatment of AD. The results may also provide clues into identification of new targets and strategies for prevention and therapy of T2D that predisposes to AD.

Episodic memory effects of gamma frequency precuneus transcranial magnetic stimulation in Alzheimer's disease: A randomized multiple baseline study.

Episodic memory decline is the prominent neuropsychological feature of typical Alzheimer's Disease (AD), for which current treatments have a limited clinical response. Recently, gamma entrainment therapy has been used as a non-invasive treatment in AD, providing evidence that it may have the potential to alleviate brain pathology and improve cognitive function in AD patients. At the same time, the precuneus (PC) has been recognized as a key area involved in AD related memory deficits and as a key node of the Default Mode Network. This study aimed to investigate the effectiveness of a 40 Hz Transcranial Magnetic Stimulation (TMS) intervention, delivered bilaterally to the precuneus for 10 days, in improving the patients' episodic memory performance. Secondary outcome variables investigated included general cognitive function, semantic and spatial memory, as well as attention and executive function. A concurrent multiple baseline design across five cases was employed. Four patients completed the study. Visual analysis combined with effect size indices were used to evaluate changes across phases. An increase in the average level of immediate recalled words was observed in three out of four patients. Effect size indices indicated significant improvement of attention skills in two patients. No treatment effect was observed for semantic and visual memory, or for executive function. An immediate treatment effect was observed in all patients' general cognitive function as assessed with the Alzheimer's Disease Assessment Scale (mean reduction of 5 points), which was maintained and improved further three months post-treatment. The neuropsychological evaluations indicated improved performance three months post-treatment in immediate and delayed recall, attention, phonological verbal fluency, anxiety, and neuropsychiatric symptoms. This study provides preliminary evidence for the efficacy of a novel non-pharmacological treatment using gamma-band TMS in addressing cognitive dysfunction in AD.

Comparison of Steady-State Pharmacokinetics of Donepezil Transdermal Delivery System with Oral Donepezil.

Donepezil is approved for treatment of dementia of the Alzheimer type and is currently available only in tablet forms in the United States. To compare steady-state pharmacokinetics of once-weekly 10-mg/d and 5-mg/d Corplex™ donepezil transdermal delivery systems (TDS) with once-daily 10-mg oral donepezil. Open-label, randomized, crossover study (NCT04617782) enrolled healthy participants aged 18-55 years. All participants received 5-mg/d donepezil TDS during the 5-week Period 1, followed by 10-mg/d TDS or 10-mg/d oral donepezil in the 5-week Period 2; treatments were switched in Period 3. Bioequivalence was assessed at steady state on Week 5. All 60 enrolled participants received 5-mg/d TDS, 55 received 10-mg/d TDS, and 56 received oral donepezil. Adjusted geometric mean ratio (% [90% CI]) for maximum plasma concentration and area under the plasma concentration versus time curve (0-168 h) were 88.7 (81.7-96.2) and 108.6 (100.5-117.4) for 10-mg/d and 86.1 (79.8-92.9) and 105.3 (97.6-113.6) for dose-normalized 5-mg/d TDS and were generally within the 80% -125% range for establishing bioequivalence with oral donepezil. Skin adhesion was similar for both TDSs (>80% of patches remaining ≥75% adhered throughout the wear period). Overall incidence of adverse events (AEs) was similar across treatments. Compared with 10-mg/d TDS, oral donepezil was associated with higher incidence of gastrointestinal and nervous system AEs (14.5% versus 53.6% and 14.5% versus 30.4%, respectively). Donepezil TDSs are bioequivalent to oral donepezil at steady state and have a safety profile that supports their use in treating dementia of the Alzheimer type.

Oral environment and cerebral blood flow in patients with neurodegenerative dementia: comparison of Alzheimer type dementia and dementia with Lewy bodies.

The number of patients with dementia is increasing worldwide. Modifying risk factors may significantly reduce the prevalence and cost of dementia. The number of remaining teeth, occlusal force, denture use, and periodontal disease status are associated with the risk of developing dementia. The oral environment may be a risk factor for dementia. This study aimed to investigate the association between the oral environment and cerebral blood flow in patients with mild cognitive impairment and dementia (either Alzheimer type dementia (ATD) or dementia with Lewy bodies (DLB)). We aimed to identify differences in the oral environment according to the underlying neurodegenerative disease. The participants were 25 patients with ATD and 25 patients with DLB who visited the Department of Dementia and Geriatric Medicine, Kanagawa Dental University Hospital. Patients were diagnosed with ATD and DLB by well-trained specialists certified by the Japanese Dementia Society and categorised as Level 3 or 4 by the Functional Assessment Staging of Alzheimer Disease scale. The correlation between oral environment (number of teeth, periodontal tissue, and oral function) and cerebral blood flow in each brain area calculated by single photon emission computed tomography was examined. The DLB group showed a significant correlation between masticatory performance and cerebral blood flow in some areas, while no such correlation was observed in the ATD group. Significant correlations were found between periodontal pocket depth and bleeding on probing and cerebral blood flow in some areas in both groups, although the correlation was considerable in the ATD group. The results of this study suggest that the association between changes in the oral environment and cerebral blood flow may differ among patients with ATD and DLB, depending on the underlying causative disease.

Social cognition deficits and biometric signatures in the behavioural variant of Alzheimer's disease.

The behavioural variant of Alzheimer's disease (bvAD) is characterized by early predominant behavioural changes, mimicking the behavioural variant of frontotemporal dementia (bvFTD), which is characterized by social cognition deficits and altered biometric responses to socioemotional cues. These functions remain understudied in bvAD. We investigated multiple social cognition components (i.e. emotion recognition, empathy, social norms and moral reasoning), using the Ekman 60 faces test, Interpersonal Reactivity Index, empathy eliciting videos, Social Norms Questionnaire and moral dilemmas, while measuring eye movements and galvanic skin response. We compared 12 patients with bvAD with patients with bvFTD (n = 14), typical Alzheimer's disease (tAD, n = 13) and individuals with subjective cognitive decline (SCD, n = 13), using ANCOVAs and age- and sex-adjusted post hoc testing. Patients with bvAD (40.1 ± 8.6) showed lower scores on the Ekman 60 faces test compared to individuals with SCD (49.7 ± 5.0, P < 0.001), and patients with tAD (46.2 ± 5.3, P = 0.05) and higher scores compared to patients with bvFTD (32.4 ± 7.3, P = 0.002). Eye-tracking during the Ekman 60 faces test revealed no differences in dwell time on the eyes (all P > 0.05), but patients with bvAD (18.7 ± 9.5%) and bvFTD (19.4 ± 14.3%) spent significantly less dwell time on the mouth than individuals with SCD (30.7 ± 11.6%, P < 0.01) and patients with tAD (32.7 ± 12.1%, P < 0.01). Patients with bvAD (11.3 ± 4.6) exhibited lower scores on the Interpersonal Reactivity Index compared with individuals with SCD (15.6 ± 3.1, P = 0.05) and similar scores to patients with bvFTD (8.7 ± 5.6, P = 0.19) and tAD (13.0 ± 3.2, P = 0.43). The galvanic skin response to empathy eliciting videos did not differ between groups (all P > 0.05). Patients with bvAD (16.0 ± 1.6) and bvFTD (15.2 ± 2.2) showed lower scores on the Social Norms Questionnaire than patients with tAD (17.8 ± 2.1, P < 0.05) and individuals with SCD (18.3 ± 1.4, P < 0.05). No group differences were observed in scores on moral dilemmas (all P > 0.05), while only patients with bvFTD (0.9 ± 1.1) showed a lower galvanic skin response during personal dilemmas compared with SCD (3.4 ± 3.3 peaks per min, P = 0.01). Concluding, patients with bvAD showed a similar although milder social cognition profile and a similar eye-tracking signature to patients with bvFTD and greater social cognition impairments and divergent eye movement patterns compared with patients with tAD. Our results suggest reduced attention to salient facial features in these phenotypes, potentially contributing to their emotion recognition deficits.

Untargeted metabolomics analysis of the hippocampus and cerebral cortex identified the neuroprotective mechanisms of Bushen Tiansui formula in an aβ25-35-induced rat model of Alzheimer’s disease

Background: Bushen Tiansui Formula (BSTSF) is a traditional formulation of Chinese medicine that has been used to treat Alzheimer's disease (AD) for decades; however, the underlying mechanisms by which this formula achieves such therapeutic effects have yet to be elucidated. Prupose: To investigate the neuroprotective mechanisms of BSTSF against AD by analyzing metabolite profiles in the hippocampus and cortex of AD rats. Methods: The rat models of AD were established by the injection of Aβ25-35. The Morris water maze (MWM) test was performed to evaluate the effect of BSTSF treatment on cognitive dysfunction. Hematoxylin and eosin (HE) staining was used to assess the effect of BSTSF on typical AD pathologies. Underlying mechanisms were investigated using LC-MS/MS-based untargeted metabolomics analysis of the cerebral cortex and hippocampus. Results: BSTSF significantly improved memory deficits and the typical histopathological changes of AD rats. Untargeted metabolomics analysis showed that 145 and 184 endogenous metabolites in the cerebral cortex and hippocampus, respectively, were significantly different in the BSTSF group when compared with the AD group. The differential metabolites in the cerebral cortex were primarily involved in cysteine and methionine metabolism, while those in the hippocampus were mainly involved in d-Glutamine and d-glutamate metabolism. Conclusion: In the present study, we confirmed the neuroprotective effects of BSTSF treatment against AD using a rat model. Our findings indicate that the BSTSF-mediated protective effects were associated with amelioration of metabolic disorders in the hippocampus and cerebral cortex.

Predicting time-to-conversion for dementia of Alzheimer's type using multi-modal deep survival analysis

Dementia of Alzheimer's Type (DAT) is a complex disorder influenced by numerous factors, and it is difficult to predict individual progression trajectory from normal or mildly impaired cognition to DAT. An in-depth examination of multiple modalities of data may yield an accurate estimate of time-to-conversion to DAT for preclinical subjects at various stages of disease development. We used a deep-learning model designed for survival analyses to predict subjects’ time-to-conversion to DAT using the baseline data of 401 subjects with 63 features from MRI, genetic, and CDC (Cognitive tests, Demographic, and CSF) data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Our study demonstrated that CDC data outperform genetic or MRI data in predicting DAT time-to-conversion for subjects with Mild Cognitive Impairment (MCI). On the other hand, genetic data provided the most predictive power for subjects with Normal Cognition (NC) at the time of the visit. Furthermore, combining MRI and genetic features improved the time-to-event prediction over using either modality alone. Finally, adding CDC to any combination of features only worked as well as using only the CDC features.

A pin-based pyro-electrohydrodynamic jet sensor for tuning the accumulation of biomolecules down to sub-picogram level detection

The detection of low abundant biomarkers is of great interest in different clinical cases, such as the early diagnosis of Alzheimer's disease. Here we present what we call pin-based pyro-electrohydrodynamic jet (p-jet) sensor that can linearly tune the accumulation rate of biomolecules in tiny droplets. In this newly revealed pin-based configuration we demonstrate the ability to detect biomolecules down to sub-picogram concentration. Two different fluorescent probes at a varying number of accumulated droplets, up to 50, have been used to investigate the p-jet sensor. Moreover, a comparative study with a commercial piezo-driven bio-spotter has been performed. The spots of biomolecules exhibit high reproducibility by achieving a coefficient of variation <10%, both in diameter and fluorescence intensity, respectively. Remarkably, the spot intensity increases linearly with the number of accumulated droplets, thus showing the effective inherent additive functionality of this technique. Such accumulation effect allowed us to reach a limit of detection down to sub-picogram level. The p-jet sensor was applied to detect the Aβ1–42 protein, a typical Alzheimer's disease biomarker, through an immunoreaction protocol carried out on the p-jet spots. The results demonstrate the compatibility of the p-jet with immunoassay procedures, opening the route to the development of a highly sensitive device able to detect low abundant biomarkers for early diagnosis applications.

Clinical characteristics and genotype-phenotype correlation analysis of familial Alzheimer's disease patients with pathogenic/likely pathogenic amyloid protein precursor mutations.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with aging, environmental, and genetic factors. Amyloid protein precursor (APP) is a known pathogenic gene for familial Alzheimer’s disease (FAD), and now more than 70 APP mutations have been reported, but the genotype-phenotype correlation remains unclear. In this study, we collected clinical data from patients carrying APP mutations defined as pathogenic/likely pathogenic according to the American college of medical genetics and genomics (ACMG) guidelines. Then, we reanalyzed the clinical characteristics and identified genotype-phenotype correlations in APP mutations. Our results indicated that the clinical phenotypes of APP mutations are generally consistent with typical AD despite the fact that they show more non-demented symptoms and neurological symptoms. We also performed genotype-phenotype analysis according to the difference in APP processing caused by the mutations, and we found that there were indeed differences in onset age, behavioral and psychological disorders of dementia (BPSD) and myoclonus.

Multiple gene variants linked to Alzheimer's-type clinical dementia via GWAS are also associated with non-Alzheimer's neuropathologic entities

The classic pathologic hallmarks of Alzheimer's disease (AD) are amyloid plaques and neurofibrillary tangles (AD neuropathologic changes, or ADNC). However, brains from individuals clinically diagnosed with “AD-type” (amnestic) dementia usually harbor heterogeneous neuropathologies in addition to, or other than, ADNC. We hypothesized that some AD-type dementia associated genetic single nucleotide variants (SNVs) identified from large genomewide association studies (GWAS) were associated with non-ADNC neuropathologies. To test this hypothesis, we analyzed data from multiple studies with available genotype and neuropathologic phenotype information. Clinical AD/dementia risk alleles of interest were derived from the very large GWAS by Bellenguez et al. (2022) who reported 83 clinical AD/dementia-linked SNVs in addition to the APOE risk alleles. To query the pathologic phenotypes associated with variation of those SNVs, National Alzheimer's disease Coordinating Center (NACC) neuropathologic data were linked to AD Sequencing Project (ADSP) and AD Genomics Consortium (ADGC) data. Separate data were obtained from the harmonized Religious Orders Study and the Rush Memory and Aging Project (ROSMAP). A total of 4811 European participants had at least ADNC neuropathology data and also genotype data available; data were meta-analyzed across cohorts. As expected, a subset of dementia-associated SNVs were associated with ADNC risk in Europeans—e.g., BIN1, PICALM, CR1, MME, and COX7C. Other gene variants linked to (clinical) AD dementia were associated with non-ADNC pathologies. For example, the associations of GRN and TMEM106B SNVs with limbic-predominant age-related TDP-43 neuropathologic changes (LATE-NC) were replicated. In addition, SNVs in TNIP1 and WNT3 previously reported as AD-related were instead associated with hippocampal sclerosis pathology. Some genotype/neuropathology association trends were not statistically significant at P < 0.05 after correcting for multiple testing, but were intriguing. For example, variants in SORL1 and TPCN1 showed trends for association with LATE-NC whereas Lewy body pathology trended toward association with USP6NL and BIN1 gene variants. A smaller cohort of non-European subjects (n = 273, approximately one-half of whom were African-Americans) provided the basis for additional exploratory analyses. Overall, these findings were consistent with the hypothesis that some genetic variants linked to AD dementia risk exert their affect by influencing non-ADNC neuropathologies.

Imaging markers of cerebral amyloid angiopathy and hypertensive arteriopathy differentiate Alzheimer disease subtypes synergistically

BackgroundBoth cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy (HA) are related to cognitive impairment and dementia. This study aimed to clarify CAA- and HA-related small vessel disease (SVD) imaging marker associations with cognitive dysfunction and Alzheimer disease (AD) subtypes.MethodsA sample of 137 subjects with clinically diagnosed late-onset AD identified from the dementia registry of a single center from January 2017 to October 2021 were enrolled. Semi-quantitative imaging changes (visual rating scale grading) suggestive of SVD were analyzed singularly and compositely, and their correlations with cognitive domains and AD subtypes were examined.ResultsPatients with typical and limbic-predominant AD subtypes had worse cognitive performance and higher dementia severity than minimal-atrophy subtype patients. Deep white matter hyperintensity (WMH) presence correlated inversely with short-term memory (STM) performance. The three composite SVD scores correlated with different cognitive domains and had distinct associations with AD subtypes. After adjusting for relevant demographic factors, multivariate logistic regression (using minimal-atrophy subtype as the reference condition) revealed the following: associations of the typical subtype with periventricular WMH [odds ratio (OR) 2.62; 95% confidence interval (CI), 1.23–5.57, p = 0.012], global SVD score (OR 1.67; 95%CI, 1.11–2.52, p = 0.009), and HA-SVD score (OR 1.93; 95%CI, 1.10–3.52, p = 0.034); associations of limbic-predominant subtype with HA-SVD score (OR 2.57; 95%CI, 1.23–5.37, p = 0.012) and most global and domain-specific cognitive scores; and an association of hippocampal-sparing subtype with HA-SVD score (OR 3.30; 95%CI, 1.58–6.85, p = 0.001).ConclusionComposite SVD imaging markers reflect overall CAA and/or HA severity and may have differential associations with cognitive domains and AD subtypes. Our finding supports the possibility that the clinical AD subtypes may reflect differing burdens of underlying CAA and HA microangiopathologies.

Electric Field Effect on Inhibiting the Co-fibrillation of Amyloid Peptides by Modulating the Aggregation Pathway.

With the revelation of the close link between Alzheimer's disease (AD) and type II diabetes (T2D) and the possible assembly of multiple amyloid peptides therein, it is critical to understand and regulate the co-fibrillation pathway between related amyloid peptides. Here, we show experimentally and theoretically that electric field (EF) inhibited hybrid amyloid fibrillation of β-amyloid peptide (Aβ) and human islet amyloid peptide (hIAPP) by modulating the hetero-aggregation pathway. Experimental results confirm that the β-sheet secondary structure of amyloid peptides would be disrupted under small static EF and accompanied by transforming fibril aggregates into amorphous particles in vitro. Molecular dynamics simulations further demonstrate that even with the transformation of the secondary structure from β-sheet to random coil, the strong interaction between Aβ and hIAPP peptides would remain largely unaffected under the small static EF, leading to the formation of amorphous nanoparticles observed in the experiments. This inhibitory effect of EF on the co-fibrillation of multiple amyloid peptides might contribute to reducing the mutual deterioration of different degenerative diseases and show great potential for the noninvasive treatment of amyloid-related diseases.

Presenilin 1 gene mutations: a potential marker to help diagnose early onset Alzheimer’s disease

Alzheimer’s disease is a prevalent neurodegenerative disorder that affects millions of people worldwide with a substantial healthcare expenditure of almost $500 billion dollars. Alzheimer’s is primarily considered a disease of the aging population, with 95% of cases being diagnosed in patients over 65. Alzheimer’s in patients under 65 years of age are termed early onset Alzheimer’s disease (EOAD). The clinical presentation and disease mechanism of EOAD are quite distinct from typical Alzheimer’s. For example, EOAD patients often experience more rapid cognitive decline and have cortical region atrophy as opposed to temporal region atrophy. The atypical nature of EOAD frequently leads to delayed diagnosis and treatment. This delay is especially problematic for EOAD patients because they are at a stage of life with significant responsibilities such as maintaining their careers and families. This case study examines a previously healthy 32-year-old man that was mistakenly suspected of having frontotemporal dementia. Alzheimer’s was not considered as a correct diagnosis due to the atypical symptoms and weak family history for the disease. For these reasons, genetic analysis was not used to help make a diagnosis. The patient died at the age of 36 and autopsy revealed markers of Alzheimer’s including neuritic plaques and tau neurofibrillary tangles. Genetic analysis revealed no presenilin 1 (PSEN1) mutations which has been associated with EOAD. However, this patient may have had deletion mutations that could not be investigated due to the lack of frozen tissue for RNA analysis. This case illustrates the importance of genetic testing for EOAD diagnosis.

The Clinical Use of Alzheimer's Disease Biomarkers in Patients with Mild Cognitive Impairment: A European Alzheimer's Disease Consortium Survey.

Background:Recent advances occurred in the field of Alzheimer’s disease (AD) biomarkers and the introduction of a research framework grounded on a biomarker-based definition of AD might have fostered an increased clinical use of AD biomarkers. For this reason, an up-to-date depiction of the clinical use of AD biomarkers is needed.Objective:To investigate the clinical use of the main AD biomarkers in patients with mild cognitive impairment (MCI) by examining the beliefs and preferences of professionals (clinicians and biomarker experts) of the European Alzheimer’s Disease Consortium (EADC).Methods:150 professionals filled in an online survey from May to September 2020. The investigated biomarkers were medial temporal lobe atrophy score (MTA) on structural MRI, typical AD (i.e., temporoparietal and posterior cingulate) hypometabolism on FDG-PET, CSF (Aβ42, p-tau, t-tau), amyloid-PET and tau-PET.Results:The frequency of responders reporting a frequent-to-constant use of MTA (77%) is higher than that of those reporting a frequent-to-constant use of the other AD biomarkers (i.e., CSF: 45%, p = 0.014; FDG-PET: 32%, p < 0.001; amyloid-PET: 8%, p < 0.001; and tau-PET: 2%, p < 0.001). CSF is considered the most valuable biomarker in terms of additional diagnostic value, followed by amyloid-PET, tau-PET, and typical AD hypometabolism on FDG-PET.Conclusion:AD biomarkers are widely used across European memory clinics with a clinical research background for the diagnosis of MCI. Overall, we observed that CSF is currently considered as the most useful biomarker, followed by amyloid-PET.

Neuroprotective effect of derris indica seed extract attenuates amyloid beta plaques induce Alzheimer’s in mice model

The progression of Alzheimer's disease type dementia is carried on by the neurotoxic effects of amyloid beta (Aβ25-35) peptide accumulation. The hypothalamic-pituitary-adrenal(HPA) axis malfunctions and leads to higher levels of amyloid beta(Aβ) accumulation. In this work, we looked at how Derris indica extract affected mice brains that had undergone neurodegeneration caused by the Aβ. Derris indica seed extract(DISE) were administered to mice over the course of 21 days in two dosages (50 mg/kg and 100 mg/kg). On the 21st day, tests for spatial learning, habituation memory, short-and long-term memory, and stepdown inhibitory responses were carried out. Pro-and anti-inflammatory cytokines and antioxidants were assessed in brain tissues. A significant (p&lt;0.01) improvement in habituation memory and the step-down inhibitory avoidance test was seen after receiving the DISE therapy, reduced escape delay considerably (p&lt;0.01) enhanced cognitive progress in spatial learning. DISE may have an impact on neuroprotection as seen by the significant (p&lt;0.01) decrease in proinflammatory and enhancement in IL-10 along with improved antioxidant indicators. According to investigations, the DISE enhance cognition by controlling neuro-inflammation and neuroimmune function, which are both controlled by the HPA axis, which mitigates stress. DISE might be promising therapeutics for neurodegeneration disorders such as AD.

Diagnosis of Alzheimer's disease: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

This paper presents the consensus of the Scientific Department of Cognitive Neurology and Aging from the Brazilian Academy of Neurology on the diagnostic criteria for Alzheimer's disease (AD) in Brazil. The authors conducted a literature review regarding clinical and research criteria for AD diagnosis and proposed protocols for use at primary, secondary, and tertiary care levels. Within this clinical scenario, the diagnostic criteria for typical and atypical AD are presented as well as clinical, cognitive, and functional assessment tools and complementary propaedeutics with laboratory and neuroimaging tests. The use of biomarkers is also discussed for both clinical diagnosis (in specific conditions) and research.

Diagnóstico da doença de Alzheimer: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia

ABSTRACT This paper presents the consensus of the Scientific Department of Cognitive Neurology and Aging from the Brazilian Academy of Neurology on the diagnostic criteria for Alzheimer’s disease (AD) in Brazil. The authors conducted a literature review regarding clinical and research criteria for AD diagnosis and proposed protocols for use at primary, secondary, and tertiary care levels. Within this clinical scenario, the diagnostic criteria for typical and atypical AD are presented as well as clinical, cognitive, and functional assessment tools and complementary propaedeutics with laboratory and neuroimaging tests. The use of biomarkers is also discussed for both clinical diagnosis (in specific conditions) and research.

Amyloid Polypeptide Disaggregation Activity of Passion Fruit Seed-Derived Polyphenol Compounds

In an aging society, the prevalence of Alzheimer disease (AD) and type 2 diabetes (T2D) has increased. It is currently hypothesized that these diseases are caused by the aggregation of amyloid β (Aβ) in the brain and human islet amyloid polypeptide (hIAPP) in the islets of Langerhans, respectively. Therefore, the disaggregation of these existing amyloid aggregates is a promising approach to the prevention and treatment of both diseases. In our previous studies, we found a remarkable Aβ and hIAPP aggregation inhibitory activity of polyphenolic compounds containing catechol moieties. Compared to previous reports on their aggregation inhibitory activity, there are few on the disaggregation activity of polyphenolic compounds. Additionally, there are few findings on the disaggregation activity of polyphenolic compounds on hIAPP. In this study, we investigated the Aβ and hIAPP disaggregation activity of scirpusin B, a polyphenolic compound found in passion fruit seeds, and related compounds. Thioflavin T (Th-T) assays and transmission electron microscopy (TEM) were performed on these compounds to evaluate their Aβ42 and hIAPP disaggregation activities. The results showed that scirpusin B and its related compounds showed remarkable disaggregation activity. The structure–activity relationship of these compounds revealed that the presence of catechol moieties is important for this activity. This study also showed that polyphenols from passion fruit seeds have significant disaggregation activity against amyloid polypeptide aggregation.