Risk Factor For Alzheimer's Disease Research Articles

X-chromosome-wide association study for Alzheimer's disease.

Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer's Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10-8) but identified seven X-chromosome-wide significant loci (P ≤ 1.6 × 10-6). The index variants were common for the Xp22.32, FRMPD4, DMD and Xq25 loci, and rare for the WNK3, PJA1, and DACH2 loci. Overall, this well-powered XWAS found no genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations.

Regional cerebral blood flow reflects both neurodegeneration and microvascular integrity across the Alzheimer's continuum.

Alzheimer's disease (AD) typically involves both neurodegenerative and vascular pathologies, each associated with reductions in cerebral blood flow (CBF). However, it remains unclear whether vascular and neural contributions to regional CBF can be differentiated. Using 3D background-suppressed arterial spin labeled perfusion magnetic resonance imaging, we evaluated regional CBF in a cohort of 257 participants across the AD continuum and assessed the impact of risk factors for both AD and small vessel disease (SVD) on regional CBF. Vascular risk factors (VRFs) were associated with reduced CBF in normal-appearing periventricular white matter, while amyloid positivity was associated with reduced CBF in the posterior cingulate cortex and precuneus. Putative SVD-sensitive regions in white matter exhibited diagnosis-related CBF changes comparable to those in typical AD cortical regions. Spatial patterns of hypoperfusion may differentiate AD and VRF-related effects on regional CBF. Our findings also support the contribution of SVD in AD pathogenesis. We used 3D background-suppressed pCASL MRI to evaluate CBF across the AD continuum. Putative SVD-sensitive regions in white matter exhibited diagnosis-related CBF changes. AD and/or SVD risk correlated with reduced CBF in AD and/or SVD-related regions. VRFs were associated with more widespread CBF reductions than amyloid positivity. Spatial patterns of hypoperfusion may differentiate AD and VRF-related effects.

CRISPR/Cas9 Gene Editing: A Novel Approach Towards Alzheimer's Disease Treatment.

In defiance of the vast amount of information regarding Alzheimer's disease (AD) that has been learned over the past thirty years, progress toward developing an effective therapy has been difficult. A neurological ailment that progresses and cannot be reversed is Alzheimer's disease, which shows neurofibrillary tangles, beta-amyloid plaque, and a lack of cognitive processes that is created by tau protein clumps with hyperphosphorylation that finally advances to neuronal damage without a recognized treatment, which has stimulated research into new therapeutic strategies. The protein CAS9 is linked to CRISPR, which is a clustered Regularly Interspaced Short Palindromic Repeat that inactivates or corrects a gene by recognizing a gene sequence that produces a doublestranded break has enchanted a whole amount of interest towards its potency to cure gene sequences in AD. The novel CRISPR-Cas9 applications for developing in vitro and in vivo models to the benefit of AD investigation and therapies are thoroughly analyzed in this work. The discussion will also touch on the creation of delivery methods, which is a significant obstacle to the therapeutic use of CRISPR/Cas9 technology. By concentrating on specific genes, such as those that are significant early- onset AD risk factors and late-onset AD risk factors, like the apolipoprotein E4 (APOE4) gene, this study aims to evaluate the potential application of CRISPR/Cas9 as a possible treatment for AD.

Risk factors for Alzheimer's disease and related dementias in U.S. honor cultures

Risk factors for Alzheimer's disease and related dementias in U.S. honor cultures

The Relationship between Framingham Stroke Risk Profile on Incident Dementia and Alzheimer's Disease: A 40-Year Follow-Up Study Highlighting Female Vulnerability.

Sex differences in the association between cardiovascular risk factors and the incident all-cause dementia and the subtype Alzheimer's disease (AD) risk are unclear. Framingham Heart Study (FHS) participants (n = 4,171, 54% women, aged 55 to 69 years) were included at baseline and followed up to 40 years. The Framingham Stroke Risk Profile (FSRP) was dichotomized into 2 levels (cutoff: 75th percentile of the FSRP z-scores). Cause-specific hazard models, with death as a competing event, and restricted mean survival time (RMST) model were used to analyze the association between FSRP levels and incident all-cause dementia and AD. Interactions between FSRP and sex were estimated, followed by a sex-stratified analysis to examine the sex modification effect. High FSRP was significantly associated with all-cause dementia (hazard ratio [HR] = 1.25, robust 95% confidence interval [CI] = 1.21 to 1.29, p < 0.001) and AD (HR = 1.58, robust 95% CI = 1.57 to 1.59, p < 0.001) in cause-specific hazard models. High FSRP was significantly associated with incident dementia (HR = 2.81, robust 95% CI = 2.75 to 2.87, p < 0.001) and AD (HR = 2.96, robust 95% CI = 2.36 to 3.71, p < 0.001) in women, but not in men. Results were consistent in the RMST models. Current diabetes and high systolic blood pressure as FSRP components were significantly associated with dementia and AD in women but not in men. High FSRP in mid- to early late life is a critical risk factor for all-cause dementia and AD, particularly in women. Sex-specific interventions and further research to elucidate underlying mechanisms are warranted. ANN NEUROL 2024;96:1124-1134.

Conceptual Framework for African American Kinship Caregiver’s Susceptibility to Alzheimer’s Disease

Kinship caregivers (e.g., grandparents raising grandchildren) have been increasing over the last several decades. Approximately 3.5 million grandparents and other relatives are the primary caregivers for their related children, and African Americans are more likely to be kinship caregivers than persons from other groups. Kinship caregivers face unique challenges, such as parenting for uncertain periods of time and often with insufficient financial resources and support, placing them at significant risk of stress. Given the findings linking chronic stress to Alzheimer’s disease (AD), there is a need for research to identify possible stressors and mitigate risks for outcomes such as AD among kin caregivers. Additionally, research indicates that African Americans (AAs) experience unusually high levels of stress due to factors often associated with structural racism, and they are disproportionately affected by cardiovascular disease (CVD), which is often a consequence of stress and another risk factor for AD. Regrettably, AA kin caregivers often incur a host of negative stress-related outcomes, including poor physical and mental health. Thus, there is an urgent need for research to identify modifiable risk factors for both stress and CVD to potentially mitigate the onset of AD in this population. The purpose of this paper is to provide a conceptual framework to examine the links between African Americans who commit to the unselfish act of providing kinship caregiving and their susceptibility to AD. Future research should investigate modifiable mechanisms to reduce the risks of AD in African American caregivers.

Protective effects of geraniol in a male rat model of Alzheimer's disease: A behavioral, biochemical, and histological study.

Alzheimer's disease (AD) as a neurodegenerative disease can cause behavioral impairments due to oxidative stress. Aging and oxidative conditions are some AD risk factors. We assessed the influence of geraniol (GR), an acyclic monoterpene alcohol, on behavioral functions, hippocampal oxidative status, and histological alterations in AD rats induced by amyloid-β (Aβ). Male Wistar rats (n = 70) were randomly allocated to the control, sham, AD, control-GR (100 mg/kg; per oral: P.O.), AD-GR (100 mg/kg; P.O.; treatment), GR-AD (100 mg/kg; P.O.; pretreatment), and GR-AD-GR (100 mg/kg; P.O.; pretreatment + treatment) groups. GR administration was done for four continuous weeks. After treatments, novel object recognition (NOR) and Morris water maze (MWM) tests assessed the animals' behavior. Then, hippocampal specimens were collected for biochemical assessment. Finally, the number of intact neurons was identified in the hippocampus using hematoxylin and eosin staining. Aβ microinjection increased learning and memory deficits in both NOR and MWM tests, oxidative stress status, and neuronal loss. Oral GR administration improved behavioral deficits and reduced oxidative stress status and neuronal loss in the Aβ-infused animals. GR ameliorates behavioral impairments through a decrease in neuronal degeneration and oxidative stress.

Cordia dichotoma G. Forst fruit prophylactic against Alzheimer's risk factors: in vitro study

Cordia dichotoma G. Forst fruit prophylactic against Alzheimer's risk factors: in vitro study

Klebsiella pneumoniae infection increases risk of Alzheimer's Disease in the UK Biobank cohort.

Infections, including bacterial pathogens, have been implicated in Alzheimer's disease (AD) risk. Klebsiella pneumoniae (K. pneumoniae) is a common hospital-acquired pathogen associated with significant inflammation, which may contribute to neurodegeneration. This study investigates the relationship between K. pneumoniae infections and AD in the UK Biobank cohort. Using UK Biobank data, we assessed AD diagnoses based on linked healthcare records and identified K. pneumoniae infections using ICD-10 codes B96.1 and J15.0. A cohort of 502,494 participants was analyzed for AD incidence in relation to demographic factors, educational years, APOE isoforms, and history of K. pneumoniae infection. Logistic regression was used to assess the association between K. pneumoniae infection and AD risk. AD incidence was significantly higher among participants with a history of K. pneumoniae infection (1.0%) compared to those without (0.2%; p < 0.001, Fisher's exact test two tailed). Logistic regression analysis revealed that K. pneumoniae infection was associated with an increased risk of AD (OR = 3.32, p < 0.001), independent of age, sex, education, and APOE isoform. Additionally, AD risk was higher among ε4ε4 carriers and increased with age but decreased with additional years of education. Our findings suggest that K. pneumoniae infection may be an independent risk factor for AD. This association underscores the need for further research into infection control and its role in mitigating neurodegenerative disease risk, particularly in populations susceptible to healthcare-associated infections. Klebsiella pneumoniae infection increases risk of Alzheimer's Disease. The gut-brain axis may be involved.

Research progress on the association of insulin resistance with type 2 diabetes mellitus and Alzheimer's disease.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that is characterized by insulin resistance and hyperglycemia. It is also known to be a risk factor for Alzheimer's disease (AD). Insulin plays a crucial role in regulating the body's metabolism and is responsible for activating the Phosphoinotide-3-Kinase (PI3K)/Protein Kinase B (Akt) signaling pathway. This pathway is activated when insulin binds to the insulin receptor on nerve cells, and it helps regulate the metabolism of glucose and lipids. Dysfunction in the insulin signaling pathway can lead to a decrease in brain insulin levels and insulin sensitivity, thereby inducing disruptions in insulin signal transduction and leading to disorders in brain energy metabolism. Moreover, these dysfunctions also contribute to the accumulation of β-amyloid (Aβ) deposition and the hyperphosphorylation of Tau protein, both of which are characteristic features of AD. Therefore, this article focuses on insulin resistance to reveal the complex mechanism between brain insulin resistance and AD occurrence in T2DM. On this basis, this article further summarizes the biological effects and mechanisms of antidiabetic drugs on the two diseases, aiming to provide new ideas for the discovery of drugs for the treatment of T2DM combined with AD.

Periodontitis associated with brain function impairment in middle-aged and elderly individuals with normal cognition.

The present study aimed to investigate changes in intranetwork functional connectivity (FC) and internetwork FC in middle-aged and elderly individuals with normal cognition (NC) and varying degrees of periodontitis to determine the effects of periodontitis on brain function. Periodontal findings and resting-state functional magnetic resonance imaging data were acquired from 51 subjects with NC. Independent component analysis and correlation analysis were used for the statistical analysis of the data. Differences in intranetwork FC were observed among groups in the anterior default-mode network (aDMN), dorsal attention network and dorsal sensorimotor network (dSMN). Compared with the nonperiodontitis (NP) group or the mild-periodontitis group, the analysis of internetwork FC showed increased FC between the auditory network and the ventral attention network (VAN), between the aDMN and the salience network (SN), and between the SN and the VAN and decreased FC between the posterior default-mode network and the right frontoparietal network in the moderate-to-severe periodontitis group. Additionally, internetwork FC between the dSMN and the VAN was also increased in the moderate-to-severe periodontitis group compared to the NP group. The altered intra- and internetwork FC were significantly correlated with the periodontal clinical index. Our results confirmed that periodontitis was associated with both intra- and internetwork FC changes even in NC. The present study indicates that periodontitis might be a potential risk factor for brain damage and provides a theoretical clue and a new treatment target for the early prevention of Alzheimer disease. Recent research has proposed that periodontitis is a potential risk factor for Alzheimer disease (AD). However, the relationship between periodontitis and the brain function of middle-aged and elderly individuals with normal cognition (NC) remains unclear. Analyzing the effect of periodontitis on brain function in the NC stage can provide clues to AD development and help achieve early prevention of dementia. The present study aimed to investigate changes in brain functional connectivity (FC) in NC with different severity of periodontitis to determine the effects of periodontitis on brain function. Both changed intranetwork FC and internetwork FC were found in the moderate-to-severe periodontitis group, and periodontitis was associated with brain network function impairment in NC. The present study indicates that periodontitis might be a potential risk factor for brain damage even in NC stage, and provides a theoretical clue and a new treatment target for the early prevention of AD.

Analysis of the Correlation Between Toxoplasma gondii Seropositivity and Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial brain disorder and infectious diseases are considered as one of the predisposing factors for AD. Toxoplasma gondii, an obligate intracellular parasitic protozoan, is suspected of being associated with AD. Serum samples were collected from 109 AD patients and 114 age-matched healthy controls. ELISA was performed using recombinant T. gondii cyst wall protein 1 (CST1) to detect T. gondii antibodies. A parallel experiment was performed with Toxoplasma gondii tachyzoites lysate protein. To analyze whether factors associated with the onset of AD included chronic T. gondii infection, a multivariate logistic regression model was applied, further validating the correlation between chronic T. gondii infection and AD. AD patients exhibited significantly higher levels of Toxoplasma-specific antibodies in their serum compared to the control group, with statistically significant differences (p < 0.05). Multivariate logistic regression analysis revealed that Toxoplasma infection is a risk factor for AD (p < 0.01), and the CST1 antigen can significantly improve the model's performance in predicting the occurrence of AD. The results indicate that chronic infection with Toxoplasma gondii could be one of the risk factors for the development of AD, potentially predisposing individuals with underlying health conditions to the disease. This further validates the correlation between Toxoplasma gondii and AD.

Sex hormone deficiency in male and female mice expressing the Alzheimer’s disease-associated risk-factor TREM2 R47H variant impacts the musculoskeletal system in a sex- and genotype-dependent manner

Abstract The R47H variant of the Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) is a risk factor for Alzheimer’s disease in humans and leads to lower bone mass accrual in female but not male 12-month-old mice. To determine whether, as with aging, gonadectomy results in sex-specific musculoskeletal effects, gonad removal or SHAM surgery were performed in 4-month-old TREM2R47H/+ mice and wild type (WT) male and female littermates (n = 10-12/group), with sexes analyzed separately. Body weight was lower in males, but higher in females after gonadectomy, independently of their genotype. Gonadectomy also lead to decreased BMD in males at all sites and in whole body (total) and spine in female mice for both genotypes. Total and femur BMD was lower in gonadectomized male mice 6-weeks post-surgery, independently of the genotype. On the other hand, BMD was only lower in ovariectomized WT but not TREM2R47H/+ mice in all sites measured at this time point. Bone formation and resorption markers levels were not affected by orchiectomy, whereas CTX was higher 3 weeks after surgery and P1NP showed a tendency towards lower values at the 6 weeks timepoint only in ovariectomized WT mice. μCT analyses showed no differences resulting from gonadectomy in structural parameters in femoral cortical bone for either sex, but lower tissue mineral density in males of either genotype 6 weeks post-surgery. Nevertheless, biomechanical properties were overall lower in gonadectomized males of either genotype, and only for WT ovariectomized mice. Distal femur cancellous bone structure was also affected by gonadectomy in a genotype- and sex-dependent manner, with genotype-independent changes in males, and only in WT female mice. Thus, expression of the TREM2 R47H variant minimally alters the impact of gonadectomy in the musculoskeletal system in males, whereas it partially ameliorates the consequences of ovariectomy in female mice.

Age-related loss of large dendritic spines in the precuneus is statistically mediated by proteins which are predicted targets of existing drugs.

Preservation of dendritic spines is a putative mechanism of protection against cognitive impairment despite development of Alzheimer Disease (AD)-related pathologies. Aging, the chief late-onset AD risk factor, is associated with dendritic spine loss in select brain areas. However, no study to our knowledge has observed this effect in precuneus, an area selectively vulnerable to early accumulation of AD-related pathology. We therefore quantified dendritic spine density in precuneus from 98 subjects without evidence of neurocognitive decline, spanning ages 20-96, and found a significant negative correlation between age and large dendritic spine density. In these same subjects, we conducted liquid chromatography-tandem mass spectrometry of >5000 proteins and identified 203 proteins which statistically mediate the effect of age on large dendritic spine density. Using computational pharmacology, we identified ten drugs which are predicted to target these mediators, informing future studies designed to test their effects on age-related dendritic spine loss and cognitive decline.

NCMP-06. GENOTYPE AND SEX IMPACT MEMORY FUNCTION AFTER BRAIN IRRADIATION

Abstract PURPOSE/OBJECTIVE Cognitive changes are a serious complication that can occur after brain radiotherapy. There is a need to better understand which individuals are more susceptible to develop strategies to preserve their function. The apolipoprotein E type 4 allele (APOEe4) APOE4 is the most prevalent genetic risk factor for Alzheimer Disease. We hypothesized that APOE genotype influences memory function after a subtherapeutic dose of whole brain irradiation in male and female mice. MATERIALS/METHODS Age-matched adult female and male mice engineered with either human APOE3 or APOE4 gene knocked-in were randomized to no treatment or whole brain irradiation (0 Gy or 5 Gy x 2), then evaluated with longitudinal neurobehavioral tests of learning, memory, pain threshold and anxiety. We performed immunohistochemical analyses of mouse brain sections at 1 month and at 4 months post-radiation to quantify extracellular amyloid beta plaques and other neuropathologic hallmarks associated with neurodegeneration. RESULTS Neurobehavioral testing identified significant sex and genotype-dependent changes in memory and anxiety measures developing longitudinally after brain irradiation. At baseline (unirradiated), APOE4 mice (male and female) performed worse on multiple memory measures. However after irradiation, sex and genotype each independently impacted multiple neurobehavioral function tests and also interacted with each other to significantly influence the timing and magnitude of changes in memory function. ApoE4 significantly impacted the toxicity of radiation in a sex-dependent manner. Neuropathologic analyses including amyloid beta plaque deposition and ApoE levels are ongoing. CONCLUSIONS After brain irradiation of relatively moderate dose, neurobehavioral performance including memory are impacted in a genotype and sex-dependent manner and dynamically over time. In addition to suggesting important sex-dependent differences in memory vulnerability, these data point to new opportunities for personalizing care for patients receiving brain irradiation.

Meta-analysis reveals an inverse relationship between Alzheimer’s disease and cancer

Recent reports have suggested an inverse relationship between Alzheimer's disease (AD) and cancer, although the underlying mechanism remains unclear. We performed an epidemiological meta-analysis to assess cancer likelihood in AD patients and vice versa and explored the role of APOE in tumor immunity across 33 The Cancer Genome Atlas (TCGA) cancer types. Our analysis revealed that people with AD are epidemiologically less likely to develop cancer than individuals without AD (RR: 0.53), and cancer patients are less likely to develop AD than non-cancer patients (RR: 0.61). Notably, APOE expression was positively associated with anti-tumor immune signatures and prevalent in early-stage tumors. This research reveals that AD patients are less likely to develop cancer and vice versa, pinpoints APOE gene as a risk factor for AD with anti-tumor activity, and provides new insight into the epidemiologically observed inverse relationship between both diseases.

Association analyses of nutritional markers with Parkinson’s disease and Alzheimer’s disease

IntroductionParkinson’s disease (PD) and Alzheimer’s disease (AD) are common neurodegenerative diseases with multifaceted etiology. Nutritional and metabolic abnormalities are frequently implicated in PD and AD. In this observational study, we analyzed a series of nutritional markers, and aimed to understand their association with AD and PD risk. MethodsA total of 424 PD patients, 314 AD patients, and 388 healthy controls were included. Nutritional markers including Hemoglobin A1c, vitamin B12, folate, apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), low-density lipoprotein (LDL), high-density lipoprotein, triglyceride, total cholesterol (TC), uric acid and homocysteine (HCY) were measured. Significance for odds ratios examining was P < 0.0045 after bonferroni correction. ResultsMultifactor risk analysis showed that ApoB, LDL, and TC reduce PD risk, while HCY increase PD risk. ApoA1 and HCY are protective and risk factors for AD, respectively. ConclusionThe cross-sectional study demonstrates that HCY and lipid metabolism markers are associated with PD and AD risks. Our findings support the involvement of one-carbon metabolism and lipid metabolism disturbance in PD and AD.

ApoE Gene Polymorphism and Clinical, Biochemical, and Sociodemographic Characteristics of Alzheimer's Disease Patients From Northern and Southern Regions of Kazakhstan.

Alzheimer's disease (AD) is the most frequent cause of dementia in seniors and is also one of the critical social issues of modern healthcare. Since AD is considered a multifactorial disease, the significance of particular risk factors in different ethnic populations is constantly reevaluated. The study group consisted of 181 patients with AD, and the control group included 244 healthy seniors comparable in sex and age to the dementia group. Our study compared clinical data, blood biochemical parameters, various sociodemographic characteristics, and ApoE gene polymorphism in patients diagnosed with AD from Kazakhstan's north (Astana city) and south (Almaty city) regions. In our cohort, significant dementia-associated variables included smoking, clinically significant depression, dyslipidemia, impaired glucose metabolism, insulin resistance, and liver dysfunction. Notably, AD patients had higher HDL levels, lower ALT levels, and higher total bilirubin and AST/ALT ratios. The ApoE ɛ4 genotype, a well-known AD risk factor, was more prevalent in the northern AD group. Additionally, participants from Astana city had a higher incidence of strokes, potentially linked to elevated LDL levels, while Almaty city residents exhibited a higher prevalence of clinically severe depression. These findings underscore the importance of considering bio-geographic and environmental factors in AD research. The study's outcomes may aid in further research and the development of personalized approaches for managing and treating AD in distinct geographical regions.

TRPV1 alleviates APOE4-dependent microglial antigen presentation and T cell infiltration in Alzheimer's disease

BackgroundPersistent innate and adaptive immune responses in the brain contribute to the progression of Alzheimer’s disease (AD). APOE4, the most important genetic risk factor for sporadic AD, encodes apolipoprotein E4, which by itself is a potent modulator of immune response. However, little is known about the immune hub that governs the crosstalk between the nervous and the adaptive immune systems. Transient receptor potential vanilloid type 1 (TRPV1) channel is a ligand-gated, nonselective cation channel with Ca2+ permeability, which has been proposed as a neuroprotective target in AD.MethodsUsing Ca2+-sensitive dyes, dynamic changes of Ca2+ in microglia were measured, including exogenous Ca2+ uptake and endoplasmic reticulum Ca2+ release. The mRFP-GFP-tagged LC3 plasmid was expressed in microglia to characterize the role of TRPV1 in the autophagic flux. Transcriptomic analyses and flow cytometry were performed to investigate the effects of APOE4 on brain microglia and T cells from APOE-targeted replacement mice with microglia-specific TRPV1 gene deficiency.ResultsBoth APOE4 microglia derived from induced pluripotent stem cells of AD patients and APOE4-related tauopathy mouse model showed significantly increased cholesterol biosynthesis and accumulation compared to their APOE3 counterparts. Further, cholesterol dysregulation was associated with persistent activation of microglia and elevation of major histocompatibility complex II-dependent antigen presentation in microglia, subsequently accompanied by T cell infiltration. In addition, TRPV1-mediated transient Ca2+ influx mitigated cholesterol biosynthesis in microglia by suppressing the transcriptional activation of sterol regulatory element-binding protein 2, promoted autophagic activity and reduced lysosomal cholesterol accumulation, which were sufficient to resolve excessive immune response and neurodegeneration in APOE4-related tauopathy mouse model. Moreover, microglia-specific deficiency of TRPV1 gene accelerated glial inflammation, T cell response and associated neurodegeneration in an APOE4-related tauopathy mouse model.ConclusionsThe findings provide new perspectives for the treatment of APOE4-dependent neurodegeneration including AD.

Long‐Term Monitoring of ApoE4 within Aqueous Humor Using Intraocular Lenses Containing Target‐Responsive Inverse Opal Hydrogel

Neurodegenerative diseases, including Alzheimer's disease (AD), pose significant challenges to global healthcare because of their irreversible postsymptomatic progression. Conventional radiographic techniques have limitations in early detection, owing to the time lapse between symptom recognition by individuals and precise inspection using medical instruments. Current research explores ophthalmic approaches to address this gap, investigating the physiological link between ocular health and brain diseases. Intraocular lenses (IOLs), widely used in cataract and refractive surgeries, provide a safe and minimally invasive platform for the continuous monitoring of neurodegenerative disease biomarkers, including those associated with AD. By integrating biomolecule‐responsive sensors with IOLs, it becomes feasible to achieve early diagnosis and long‐term, noninvasive monitoring postimplantation. Herein, a fluorescently labeled inverse opal hydrogel (FIOH) is merged with IOLs for ApoE4 detection, a key risk factor for AD. The permeability and inherent photonic properties of FIOH facilitate the cumulative enhancement of the fluorescence signal. In a simulation of the aqueous humor circulation, the detection limit for ApoE4 is determined to be 0.1 nM. Therefore, FIOH‐integrated IOLs hold promise not only for early detection but also for providing a reliable platform for the continuous, noninvasive monitoring of neurodegenerative diseases after the initial, minimally invasive implantation.