CD147 associates cerebrovascular lesion with Aβ pathology in Alzheimer’s disease
Feng Gao, Yaxi Zhan, Qiong Wang, Linbin Dai, Yong Shen,- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Cerebrovascular abnormality is recognized as a major contributor to Alzheimer’s disease (AD). However, how cerebrovascular damage accelerates Aβ production/deposition remains poorly defined. CD147, a transmembrane molecule mainly expressed in cerebral small vessels, modulates γ secretase function and Aβ production in vitro. The present study was to study whether CD147 associated cerebrovascular damage with the Aβ pathology in autopsied human brains with AD, and whether CD147 in the CSF was related with CSF Aβ AD patients from China Aging and Neurodegenerative Initiative (CANDI) cohort.
Method
Amounts of soluble CD147, membrane CD147 / Claudin‐5 / CD31 and insoluble Aβ43 /42 /40 from autopsied human brain tissue samples were assessed by ELISA, Luminex and MSD, respectively. In CANDI cohort, CSF Aβ40 and 42, CSF CD147, CSF Aβ43, and CSFAβ38 were measure with Simoa, Luminex, ELISA, and MSD, respectively. Linear regression models were used to evaluate the associations between CSF CD147 with cognitive decline (MMSE and cortical thickness), GFAP, NFL, Aβ burden (18F‐Flobetapir), and Aβ isoforms (Aβ43/42/40/38).
Result
In autopsied human AD brains, the lower soluble/membrane CD147 ratio was significantly associated with worse BBB integrity (lower Claudin‐5/CD31 ratio) and with higher levels of insoluble Aβ43 and Aβ42. In the CANDI cohort, lower CSF CD147 in AD patients was also significantly associated with higher level of Aβ burden. Interestingly, CSF CD147 show a stronger association with shorter Aβ isoforms (Aβ38 ≈ Aβ40 > Aβ42 > Aβ43). Decreasing CSF CD147 was significantly linked to worse cognitive function (MMSE and cortical thickness) and with higher levels of CSF GFAP and NFL. White matter hyperintensity was negatively significantly associated with CSF CD147.
Conclusion
Cerebrovascular damage may impair the release of CD147 from vessels, thereby further exacerbate Aβ pathology via shifting the production of Aβ from longer to shorter isoforms. The findings suggest that soluble CD147 links cerebrovascular damage and Aβ pathology and cerebrovascular CD147 could be a potential therapeutic target for AD.