Association of small vessel disease with tau pathology

Journal Article · 18 January 2022 · Acta Neuropathologica

DOI: https://doi.org/10.1007/s00401-021-02397-x · OSTI ID:1923921

Kapasi, Alifiya  ^[1]; Yu, L. ^[1]; Petyuk, V.  ^[2]; Arfanakis, K. ^[3]; Bennett, D. A. ^[1]; Schneider, J. A. ^[1]

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1. Rush University Medical Center, Chicago, IL (United States)
2. Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
3. Rush University Medical Center, Chicago, IL (United States); Illinois Institute of Technology, Chicago, IL (United States)

Emerging evidence suggests that small vessel disease (SVD) is a risk factor for clinical dementia and may contribute to AD neuropathological changes. Watershed brain regions are located at the most distal areas between arterial territories, making them vulnerable to SVD-related changes. We examined the association of pathologic markers of SVD, specifically arteriolosclerosis in watershed brain regions, with AD pathologic changes. Participants (N= 982; mean age-at-death = 90; 69% women) were enrolled as part of one of two cohort studies of aging and dementia. At autopsy, neuropathological evaluation included semi-quantitative grading of arteriolosclerosis pathology from 2 cortical watershed regions: the anterior watershed (AWS) and posterior watershed (PWS), densities for cortical β-amyloid and tau-tangle pathology, and other common age-related pathologies. Linear regression models examined the association of watershed arteriolosclerosis pathology with β-amyloid and tau-tangle burden. In follow-up analyses, available ex-vivo MRI and proteomics data in a subset of decedents were leveraged to examine the association of whole brain measure of WMH, as a presumed MRI marker of SVD, with β-amyloid and tau-tangle burden, as well as to examine the association of watershed arteriolosclerosis with proteomic tau. Watershed arteriolosclerosis was common, with 45% of older persons having moderate-to-severe arteriolosclerosis pathology in the AWS region, and 35% in the PWS. In fully adjusted models that controlled for demographics and common age-related pathologies, an increase in severity of PWS arteriolosclerosis was associated with a higher burden of tau-tangle burden, specifically neocortical tau burden, but not with β-amyloid. AWS arteriolosclerosis was not associated with β-amyloid or tau pathology. Ex-vivo WMH was associated with greater tau-tangle pathology burden but not β-amyloid. Furthermore, PWS arteriolosclerosis was associated with higher abundance of tau phosphopeptides, that promote formation of tau aggregates. These data provide compelling evidence that SVD, specifically posterior watershed arteriolosclerosis pathology, is linked with tau pathological changes in the aging brain.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
• Sponsoring Organization: USDOE Office of Science (SC); National Institute on Aging (NIA)
• Grant/Contract Number: AC05-76RL01830
• OSTI ID: 1923921
• Report Number(s): PNNL-SA-177136
• Journal Information: Acta Neuropathologica, Journal Name: Acta Neuropathologica Journal Issue: 3 Vol. 143; ISSN 0001-6322
• Publisher: SpringerCopyright Statement
• Country of Publication: United States
• Language: English