Vascular Lesions, APOE ε4, and Tau Pathology in Alzheimer Disease

Abstract

We sought to determine the associations among cerebral amyloid angiopathy (CAA), white matter rarefaction (WMR), circle of Willis atherosclerosis (CWA), and total microinfarct number with Braak neurofibrillary stage in postmortem individuals with and without Alzheimer disease (AD). Data from 355 cases of autopsied individuals with Braak stage I–VI who had antemortem consensus diagnoses of cognitively unimpaired (n = 183), amnestic mild cognitive impairment (n = 31), and AD dementia (n = 141) were used. The association between Braak stage and vascular lesions were individually assessed using multivariable linear regression that adjusted for age at death, APOE ε4 carrier status, sex, education, and neuritic plaque density. CAA (p = 0.007) and WMR (p < 0.001) were associated with Braak stage, independent of amyloid load; microinfarct number and CWA showed no association. Analyses of the interactions between APOE ε4 carrier status and vascular lesions found that greater WMR and positive ε4 carrier status were associated with higher Braak stages. These results suggest that CAA and WMR are statistically linked to the severity of AD-related NFT pathology. The statistical link between WMR and NFT load may be strengthened by the presence of APOE ε4 carrier status. An additional finding was that Lewy body pathology was most prevalent in higher Braak stages.

Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia

“…This finding is consistent with previous reports in sporadic AD cases of increased CAA severity in this region [2], possibly related to Aβ drainage and structural characteristics of the brain vascular system. Moreover, an association between parenchymal CAA pathology, perivascular tau pathology [36], and neuronal tau pathology severity has been described [27], consistent with this case's unique pattern of pathology in which the few regions affected with CAA showed also higher tau pathology. We suggest that, even though the homozygous APOE3ch variant likely rendered general protection for tau pathology in this patient, it could not render specific protection against CAA-related tau pathology in the occipital cortex, possibly due to the local effects of CAA pathology and associated tau deposition.…”

Discovering Gene Signature Shared by Prostate Cancer and Neurodegenerative Diseases Based on the Bioinformatics Approach

“…The APOE E4 allele is a risk factor for AD and might be a risk factor for prostate cancer as well [ 34 ]. This may be related to vascular lesions, which can lead to the progression of prostate cancer and neurodegenerative disease [ 35 ]. This is consistent with the conclusion found by our enrichment analysis of co-DEGs: the mechanism of PCa progression is related to vascular smooth muscle contraction pathway and blood circulation regulation function.…”

Early-stage differentiation between Alzheimer’s disease and frontotemporal lobe degeneration: Clinical, neuropsychology, and neuroimaging features

“…In this study, we have investigated some of the demographic factors most relevant to the cognitive traits, such as age at disease onset, disease duration, and education ( Table 1 ); clinical features as motor signs and behavioral disorders ( Figure 2 ); APOE genotype ( Table 1 ) and vascular diseases and medical histories ( Figure 2 and Table 1 ). In recent years, it has been suggested that AD and FTLD might be kinds of cognitive disorder caused by both vascular pathological changes and neurodegenerative damage, especially in the AD spectrum ( Nichols et al, 2021 ). Many previous longitudinal studies have also shown that vascular risk factors (VRFs) are hazard factors for AD, such as middle-age hypertension, hypercholesteremia, diabetes, obesity, stroke, atrial fibrillation, and lack of exercise ( Yu et al, 2020 ).…”