Vascular Lesions, APOE ε4, and Tau Pathology in Alzheimer Disease
Open accessAbstract
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.
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An association between parenchymal CAA pathology, perivascular tau pathology, and neuronal tau pathology severity has been described.
“Moreover, an association between parenchymal CAA pathology, perivascular tau pathology [36], and neuronal tau pathology severity has been described [27]”
From Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia (2022) · cites this paper as [27]
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“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.”
ResultSelf-citation
- Authors
- Nichols, J. B., Malek-Ahmadi, M., Tariot, P. N., Serrano, G. E., Sue, L. I., & Beach, T. G.
- Affiliations
- Midwestern University (US)
- Banner Alzheimer’s Institute , Phoenix, Arizona, USA
- Banner Alzheimer’s Institute (US)
- Banner Sun Health Research Institute (US)
- Corresponding author
- Nichols, Jodie B
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2021-02-22
- Volume
- 80
- Issue
- 3
- Pages
- 240-246
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC7899190
- OpenAlex
- W3131445577
- Cited by
- 22
- References
- 63
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 8 · 2022: 6 · 2021: 1 · 2012: 1
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Midwestern University Kenneth A. Suarez Summer Research Fellowship
- The Brain and Body Donation Program
- National Institute of Neurological Disorders and Stroke (U24 NS072026)
- National Brain and Tissue Resource for Parkinson’s Disease and Related Disorders
- National Institute on Aging (P30 AG19610)
- Arizona Alzheimer’s Disease Core Center
- Arizona Department of Health Services (211002)
- Arizona Biomedical Research Commission (4001, 0011, 05-901, 1001)
- Arizona Parkinson's Disease Consortium
- Michael J. Fox Foundation for Parkinson’s Research
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, cerebral amyloid angiopathy, white matter rarefaction, microinfarcts, APOE ε4, tau pathology, Lewy body pathology, vascular lesions, amnestic mild cognitive impairment, neuropathology
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Circle of Willis, Female, Heterozygote, Humans, Male, Vascular Diseases, Databases, Factual, tau Proteins, Apolipoprotein E4
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