Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias

TLDR

Vascular risk factors are increasingly linked to Alzheimer’s disease. The study examined how common and severe atherosclerotic plaques are in the circle of Willis among Alzheimer’s patients and other neurodegenerative disorders. The authors analyzed semi‑quantitative gross and microscopic neuropathology from 1,000 cases, including 410 Alzheimer’s, 230 synucleinopathies, 157 TDP‑43, 144 tauopathies, and 59 normal aging. More than 77 % of Alzheimer’s cases showed circle of Willis atherosclerosis, a higher rate than in normal aging (47 %) or other neurodegenerative diseases (43–67 %), and the atherosclerosis severity correlated with neuritic plaques, tau tangles, and cerebral amyloid angiopathy—especially in females—while showing no link to α‑synuclein or TDP‑43 lesions, supporting a specific vascular–AD relationship.

Abstract

A growing body of evidence demonstrates an association between vascular risk factors and Alzheimer's disease. This study investigated the frequency and severity of atherosclerotic plaques in the circle of Willis in Alzheimer's disease and multiple other neurodegenerative diseases. Semi-quantitative data from gross and microscopic neuropathological examinations in 1000 cases were analysed, including 410 with a primary diagnosis of Alzheimer's disease, 230 with synucleinopathies, 157 with TDP-43 proteinopathies, 144 with tauopathies and 59 with normal ageing. More than 77% of subjects with Alzheimer's disease had grossly apparent circle of Willis atherosclerosis, a percentage that was significantly higher than normal (47%), or other neurodegenerative diseases (43-67%). Age- and sex-adjusted atherosclerosis ratings were highly correlated with neuritic plaque, paired helical filaments tau neurofibrillary tangle and cerebral amyloid angiopathy ratings in the whole sample and within individual groups. We found no associations between atherosclerosis ratings and α-synuclein or TDP-43 lesion ratings. The association between age-adjusted circle of Willis atherosclerosis and Alzheimer's disease-type pathology was more robust for female subjects than male subjects. These results provide further confirmation and specificity that vascular disease and Alzheimer's disease are interrelated and suggest that common aetiologic or reciprocally synergistic pathophysiological mechanisms promote both vascular pathology and plaque and tangle pathology.