“Vascular contributions to cognitive impairment are increasingly recognized as shown by neuropathological, neuroimaging, and cerebrospinal fluid biomarker studies.”
“Moreover, small vessel disease of the brain has been estimated to contribute to approximately 50% of all dementias worldwide, including those caused by Alzheimer’s disease”.

“Vascular changes in Alzheimer’s disease have been typically attributed to the vasoactive and/or vasculotoxic effects of amyloid-β, and more recently tau.”

“….studies suggest that amyloid-β and tau lead to blood vessel abnormalities and blood–brain barrier breakdown…..neurovascular dysfunction and blood–brain barrier breakdown develop early in Alzheimer’s disease…”
“To address this question, we studied brain capillary damage using a novel cerebrospinal fluid biomarker of blood–brain barrier-associated capillary mural cell pericyte, soluble platelet-derived growth factor receptor-β, and regional blood–brain barrier permeability using dynamic contrast-enhanced magnetic resonance imaging.”
“Our data show that individuals with early cognitive dysfunction develop brain capillary damage and blood–brain barrier breakdown in the hippocampus irrespective of Alzheimer’s amyloid-β and/or tau biomarker changes, suggesting that blood–brain barrier breakdown is an early biomarker of human cognitive dysfunction independent of amyloid-β and tau.”
D.A.Nation, et al
Blood–brain barrier breakdown is an early biomarker of human cognitive dysfunction
Nature Medicine — Volume 25 #2 — February 2019 — page 270