An analysis of cerebral amyloid angiopathy based on samples from human brain bank

Abstract

Background Cerebral amyloid angiopathy (CAA) is a common age-associated cerebrovascular disease marked by amyloid-β (Aβ) accumulation in cerebral vessel walls, and it is tightly linked to Alzheimer’s disease (AD) and cognitive impairment. However, the specific mechanism in CAA progression remains poorly elucidated. Methods We analyzed 49 autopsy samples obtained from the Human Brain Bank of Hebei Medical University, collected basic pathological data and explored the correlations between CAA and Alzheimer’s disease neuropathologic change (ADNC). Transcriptomic sequencing was performed on 21 occipital lobe specimens to screen differentially expressed genes underlying CAA and its pathological subtypes. Results Neuropathological examination identified CAA pathology in 29 of 49 community donors (59.18%). Both CAA type and stage were significantly correlated with ADNC. In particular, CAA type 1 was closely associated with AD pathology and cognitive decline. Transcriptome analysis revealed that the GO functional enrichment was mainly concentrated in immune response-activating and -regulating signaling pathways. Triggering receptor expressed on myeloid cells 1 (TREM1) gene was involved in the amplification of immune signals, and it was expressed more strongly in the CAA1 subtype. Conclusion CAA is not simply an independent cerebrovascular disorder but also serves as a critical synergistic risk factor for ADNC progression. TREM1 is a potential gene that could be associated with a more severe pathological progression of CAA1 type.