Revisiting atherosclerosis and dementia

Abstract

Hardening of the arteries (atherosclerosis) was linked to dementia long ago, but subsequently, Alzheimer’s plaques and tangles have received more attention. A new proteome-wide association study unveils molecular links between intracranial atherosclerosis and dementia, independent of other pathologies, providing new evidence for one of the oldest suspected causes of dementia.

Fig. 1 |. ATS of the circle of Willis and proximal arterial branches is linked to MCI–AD through proteomic changes in the prefrontal cortex independent of tau, TDP43, Aβ, Lewy bodies, cerebral amyloid angiopathy, macro- and microinfarcts, and hippocampal sclerosis.

Tau is also independently linked to AD–MCI, through proteomic changes in part overlapping with ATS. In RNA processing and splicing, ATS and tau have opposite effects. Aβ is not directly linked to proteomic changes associated with MCI–AD, but since these data are from an autopsy study the possibility that vascular risk factors and Aβ are involved early in the disease process, for which there is biological plausibility, cannot be ruled out.