Neuropathology of Aging and Alzheimer's Disease: Chapter 10 - The role of vascular disease in Alzheimer’s disease neuropathology

Essentially all early researchers who explored the relationship between vascular disease and Alzheimer’s disease pathology (senile plaques and neurofibrillary tangles) throughout the 20th century concluded there was no relationship. Multiple-infarct dementia was specifically conceptualized as distinct from Alzheimer’s disease, while subcortical arteriosclerotic leukoencephalopathy, or so-called Binswanger’s disease, predates Alzheimer’s disease and remains distinct from it. Cerebral small-vessel disease is heterogeneous and encompasses cerebral amyloid angiopathy, so some marginal pathogenic overlap is evident in the accumulation of amyloid-β in this subset. Even then, cerebral amyloid angiopathy may occur in the absence of Alzheimer’s disease lesions, and Alzheimer’s disease lesions may be abundant with little or no cerebral amyloid angiopathy. Modern neuroimaging has renewed the interest in a link between the vasculature and hallmark lesions based on the “neurovascular unit,” although data at present permit no conclusions. Vascular cognitive impairment in the absence of end-organ damage (i.e., ischemic infarcts) remains a challenging interpretation on clinical and neuropathological grounds and might be considered additive to Alzheimer’s disease until a clearer understanding emerges. Of practical importance is the potential toxicity of recently approved anti-amyloid-β immunotherapy to patients with cerebral amyloid angiopathy.