Multimodal comparison of plasma proteins associated with blood-brain barrier impairment in Alzheimer’s disease

Background:
Vascular impairment is one of the major contributors to dementia. We aimed to identify blood biomarkers suggestive of potential impairment of the blood-brain barrier (BBB) in subjects with Alzheimer’s disease (AD).

Methods:
We used administrative data from the VA Informatics and Computing Infrastructure Resource Center to study both inpatients and outpatients with AD. Plasma samples from healthy control and AD individuals were analyzed using enzyme-linked immunosorbent assay and proteomics approaches to identify differentially expressed proteins. Bioinformatic analysis was applied to explore significantly enriched pathways.

Results:
In the same cohort of patients with AD, we found twice number of subjects with cerebral amyloid angiopathy in the two-year period after the onset of AD, compared to the number of subjects with cerebral amyloid angiopathy in the two-year period prior to AD onset. Different pathways related to BBB, like cell adhesion, extracellular matrix organization and Wnt signaling, were activated and differentially expressed proteins such as ADAM22, PDGFR-α, DKK-4, Neucrin and RSOP-1 were identified. Moreover, matrix metalloproteinase-9, which is implicated in causing degradation of basal lamina and BBB disruption, was significantly increased in the plasma of AD patients.

Conclusions:
Alteration of proteins found in AD subjects could provide new insights into biomarkers regulating permeability and BBB integrity.