Study Examines Association Between Small-Vessel Disease, Alzheimer Pathology

The patient who led to the discovery of Alzheimer disease. (Source: Wikipedia.)
The patient who led to the discovery of Alzheimer disease. (Source: Wikipedia.)

Main Point:

Cerebral small-vessel disease (SVD) and Alzheimer disease (AD) pathology appear to be associated.

Published in:

JAMA Neurology


Maartje I. Kester, M.D., Ph.D., of the VU University Medical Center, Amsterdam, the Netherlands, and colleagues.


AD is believed to be caused by the buildup of amyloid protein in the brain and tau tangles. Previous studies have suggested that SVD and vascular risk factors increase the risk of developing AD. In both SVD and vascular dementia (VaD), signs of AD pathology have been seen. But it remains unclear how the interaction between SVD and AD pathology leads to dementia.

How the Study Was Conducted:

Authors examined the association between SVD and AD pathology by looking at magnetic resonance imaging (MRI)-based microbleeds (MB), white matter hyperintensities (WMH) and lacunes (which are measures for SVD) along with certain protein levels in cerebrospinal fluid (CSF) which reflect AD pathophysiology in patients with AD, VaD and healthy control patients. The authors also examined the relationship of apolipoprotein E (APOE) Ɛ4 genotype, a well-known risk factor for AD.


The presence of both MBs and WMH was associated with lower CSF levels of Aβ42, suggesting a direct relationship between SVD and AD. Amyloid deposits also appear to be abnormal in patients with SVD, especially in (APOE) Ɛ4 carriers.


“Our study supports the hypothesis that the pathways of SVD and AD pathology are interconnected. Small-vessel disease could provoke amyloid pathology while AD-associated cerebral amyloid pathology may lead to auxiliary vascular damage.”


Maartje I. Kester MD, PhD, Jeroen D. C. Goos MD, PhD, Charlotte E. Teunissen PhD, Marije R. Benedictus MSc, Femke H. Bouwman MD, PhD, Mike P. Wattjes MD, PhD, Frederik Barkhof MD, PhD, Philip Scheltens MD, PhD, Wiesje M. van der Flier PhD. Associations Between Cerebral Small-Vessel Disease and Alzheimer Disease Pathology as Measured by Cerebrospinal Fluid Biomarkers. JAMA Neurol. 2014; 71(7):-. doi:10.1001/jamaneurol.2014.754

Editor’s Note:

The authors made conflict of interest and funding disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Media Advisory:

To contact author Maartje I. Kester, M.D., Ph.D., email

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