Age-matched Alzheimer's Disease Patients Research Articles

Brain Tissue-Derived Extracellular Vesicles in Alzheimer's Disease Display Altered Key Protein Levels Including Cell Type-Specific Markers.

Brain tissue-derived extracellular vesicles (bdEVs) play neurodegenerative and protective roles, including in Alzheimer's disease (AD). Extracellular vesicles (EVs) may also leave the brain to betray the state of the CNS in the periphery. Only a few studies have profiled the proteome of bdEVs and source brain tissue. Additionally, studies focusing on bdEV cell type-specific surface markers are rare. We aimed to reveal the pathological mechanisms inside the brain by profiling the tissue and bdEV proteomes in AD patients. In addition, to indicate targets for capturing and molecular profiling of bdEVs in the periphery, CNS cell-specific markers were profiled on the intact bdEV surface. bdEVs were separated and followed by EV counting and sizing. Brain tissue and bdEVs from age-matched AD patients and controls were then proteomically profiled. Total tau (t-tau), phosphorylated tau (p-tau), and antioxidant peroxiredoxins (PRDX) 1 and 6 were measured by immunoassay in an independent bdEV separation. Neuron, microglia, astrocyte, and endothelia markers were detected on intact EVs by multiplexed ELISA. Overall, concentration of recovered bdEVs was not affected by AD. Proteome differences between AD and control were more pronounced for bdEVs than for brain tissue. Levels of t-tau, p-tau, PRDX1, and PRDX6 were significantly elevated in AD bdEVs compared with controls. Release of certain cell-specific bdEV markers was increased in AD. Several bdEV proteins are involved in AD mechanisms and may be used for disease monitoring. The identified CNS cell markers may be useful tools for peripheral bdEV capture.

Neuropsychological Differences Related to Age in Dementia with Lewy Bodies

Background/Aims: To examine the influence of age on neuropsychological performances in dementia with Lewy bodies (DLB) and Alzheimer disease (AD) patients. Methods: We examined memory, executive, and visuo-constructional performances in 202 DLB patients and 236 AD patients. We divided the subjects into three age groups (65–74, 75–84, and 85–95 years old), and evaluated the differences in neuropsychological performances. Results: Recent memory in the DLB group was significantly better than that in the age-matched AD group when comparing the age groups 65–74 years and 75–84 years; however, memory impairment in the DLB patients in the age group 85–95 years was comparable with that in the age-matched AD patients. In contrast to recent memory, the other assessed neuropsychological performances, such as visuospatial and executive functions, showed no significant change in differences between the DLB and AD groups with advancing age. Conclusion: Our study revealed that the nature of memory impairment in DLB patients changes according to age. DLB patients in the young-old and old-old age groups showed significantly better memory performance than the age-matched AD patients, whereas memory performance of the DLB patients in the oldest-old age group was similar to that of the age-matched AD patients. This may be associated with the increased rate of coexisting AD pathology in DLB patients with older age.

Cholinergic Changes in Aging and Alzheimer Disease: An [18F]-F-A-85380 Exploratory PET Study.

The central cholinergic system undergoes changes during the physiological process of aging and the pathologic process of Alzheimer disease (AD). We aimed to analyze the impairment of cholinergic pathways by positron emission tomography using the [F]-F-A-85380 (FA85) tracer, which has a high affinity for nicotinic acetylcholine receptors (nAChRs). Aging was assessed by comparing young (n=10) and elderly (n=4) healthy subjects, and the pathologic process of AD was assessed by comparing elderly controls and age-matched AD patients (n=8). We measured an index of the nAChR density in the cortex and the hippocampus and the total number of FA85-binding sites by taking into account the volume changes. In AD, the nAChR density was preserved in both the cortex and hippocampus. The total estimated number of FA85-binding sites was decreased in the hippocampus despite the lack of a significant loss of volume, whereas the difference in the cortex did not withstand the adjustment for multiple comparisons despite a significant loss of volume. In contrast, in aging, the estimated number of FA85-binding sites was decreased in both the cortex and hippocampus with significant hippocampal atrophy. These findings suggest a preferential impairment of cholinergic pathways in the cortex during aging, whereas in AD, this damage predominated in the hippocampus with a potential compensatory cholinergic effect in the cortex.

Distribution of Amyloid Burden Differs between Idiopathic Normal Pressure Hydrocephalus and Alzheimer's Disease

This study aimed to elucidate the incidence and distribution of the cortical retention of Pittsburgh compound B (PIB) in patients with idiopathic normal pressure hydrocephalus (iNPH) and clarify the differences from those in patients with Alzheimer's disease (AD). Ten patients with iNPH without any clinical signs indicative of AD were enrolled in this study. Cerebral retention of PIB in positron emission tomography (PET) in iNPH patients was compared with those in seven age-matched AD patients. The CSF levels of β-amyloid 1-42 peptide (Aβ42), which inversely decrease with cerebral amyloid burden, were also measured. Three of the ten patients with iNPH showed increased cortical PIB retention. Although the mean cortical SUV ratios were similar, the distribution of PIB retention differed widely between the patients with iNPH and AD. PIB retention was limited to the high-convexity parasagittal areas in iNPH patients, whereas it spread over the frontal and parietotemporal areas in AD. The coronal images of PIB-PET were more informative than conventional transverse images in evaluating the distribution pattern of cortical PIB retention. Two iNPH patients with higher cortical PIB retention had the lowest levels of CSF Aβ42, indicating that PIB retention in iNPH would not reflect a simple delay in PIB clearance but its binding to existing Aβ amyloid in the brain. Our results indicate that iNPH is one of the diseases exhibiting cortical PIB retention. The characteristic distribution of PIB retention in iNPH could be useful in the differential diagnosis between iNPH and AD.

Relationships between Dehydroepiandrosterone Sulfate (DHEAS) and Cortisol (CRT) Plasma Levels and Everyday Memory in Alzheimer's Disease Patients Compared to Healthy Controls

Fifty-two age-matched Alzheimer's disease (AD) patients (26 men, 26 women), mean age 76.2 years, were assessed with the Rivermead Behavioural Memory Test, a test of everyday memory, coincident with the measurement of plasma cortisol (CRT) and dehydroepiandrosterone sulfate (DHEAS) via radioimmunoassay. The AD patients were compared to a control group of age- and gender-matched healthy elderly men and women. No differences were found between the AD patients and the controls in DHEAS or CRT levels, or in the DHEAS/CRT ratio. There were no gender differences in DHEAS or CRT levels, or in the DHEAS/CRT ratio in subjects with AD. However, AD patients with higher levels of DHEAS scored better than those with lower levels on the subtests of Remembering a Name associated with a picture, Digit Span Total and Forward, and the Mini Mental Status Exam. AD patients with higher CRT levels performed worse on Delayed Route Recall than those with lower levels. These findings suggest that AD patients with higher endogenous levels of DHEAS may perform better on some memory tasks than those with lower levels, while AD patients with lower levels of CRT may perform better than those with higher CRT.