Vascular contributions to Alzheimer's disease

Laura B Eisenmenger; Anthony Peret; Bolanle M Famakin; Alma Spahic; Grant S Roberts; Jeremy H Bockholt; Kevin M Johnson; Jane S Paulsen

doi:10.1016/j.trsl.2022.12.003

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Vascular contributions to Alzheimer's disease

Journal article

Open access

Peer reviewed

Vascular contributions to Alzheimer's disease

Laura B Eisenmenger, Anthony Peret, Bolanle M Famakin, Alma Spahic, Grant S Roberts, Jeremy H Bockholt, Kevin M Johnson and Jane S Paulsen

Translational research : the journal of laboratory and clinical medicine, Vol.254, pp.41-53

04/2023

DOI: 10.1016/j.trsl.2022.12.003

PMCID: PMC10481451

PMID: 36529160

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https://pmc.ncbi.nlm.nih.gov/articles/PMC10481451/pdf/nihms-1903933.pdfView

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Abstract

Alzheimer's disease (AD) is the most common cause of dementia and is characterized by progressive neurodegeneration and cognitive decline. Understanding the pathophysiology underlying AD is paramount for the management of individuals at risk of and suffering from AD. The vascular hypothesis stipulates a relationship between cardiovascular disease and AD-related changes although the nature of this relationship remains unknown. In this review, we discuss several potential pathological pathways of vascular involvement in AD that have been described including dysregulation of neurovascular coupling, disruption of the blood brain barrier, and reduced clearance of metabolite waste such as beta-amyloid, a toxic peptide considered the hallmark of AD. We will also discuss the two-hit hypothesis which proposes a 2-step positive feedback loop in which microvascular insults precede the accumulation of Aß and are thought to be at the origin of the disease development. At neuroimaging, signs of vascular dysfunction such as chronic cerebral hypoperfusion have been demonstrated, appearing early in AD, even before cognitive decline and alteration of traditional biomarkers. Cerebral small vessel disease such as cerebral amyloid angiopathy, characterized by the aggregation of Aß in the vessel wall, is highly prevalent in vascular dementia and AD patients. Current data is unclear whether cardiovascular disease causes, precipitates, amplifies, precedes, or simply coincides with AD. Targeted imaging tools to quantitatively evaluate the intracranial vasculature and longitudinal studies in individuals at risk for or in the early stages of the AD continuum could be critical in disentangling this complex relationship between vascular disease and AD.

Alzheimer Disease

Animals

Blood-Brain Barrier - metabolism

Brain - pathology

Cardiovascular Diseases

Cognitive Dysfunction

Equidae

Humans

Details

Title: Subtitle: Vascular contributions to Alzheimer's disease
Creators: Laura B Eisenmenger - University of Wisconsin–Madison
Anthony Peret - University of Wisconsin–Madison
Bolanle M Famakin - University of Wisconsin–Madison
Alma Spahic - University of Wisconsin–Madison
Grant S Roberts - University of Wisconsin–Madison
Jeremy H Bockholt - Georgia State University
Kevin M Johnson - University of Wisconsin–Madison
Jane S Paulsen - University of Wisconsin–Madison
Resource Type: Journal article
Publication Details: Translational research : the journal of laboratory and clinical medicine, Vol.254, pp.41-53
DOI: 10.1016/j.trsl.2022.12.003
PMID: 36529160
PMCID: PMC10481451
NLM abbreviation: Transl Res
ISSN: 1931-5244
eISSN: 1878-1810
Grant note: R01 AG075788 / NIA NIH HHS R01 AG043608 / NIA NIH HHS KL2 TR002374 / NCATS NIH HHS P30 AG062715 / NIA NIH HHS UL1 TR002373 / NCATS NIH HHS
Language: English
Date published: 04/2023
Academic Unit: Psychiatry; Psychological and Brain Sciences
Record Identifier: 9984383289002771

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