biostudies-literaturePerosa VAlzheimer's AssociationNIGMS NIH HHSNIH HHS156https://www.ebi.ac.uk/biostudies/studies/S-EPMC12265290biostudies-literatureUnknown13(1)The medial temporal lobe (MTL) is strategically important for cognition and the pathogenesis of Alzheimer's Disease (AD). Cerebral small vessel disease (CSVD) independently contributes to cognitive impairment and is believed to play a role in AD. CSVD and proteinopathies related to AD often coexist in the MTL but neither the severity of CSVD, nor the associations between these pathologies have been quantitatively addressed in this brain region. We hypothesized that the severity of CSVD in the MTL is associated with the local burden of proteinopathies implicated in neurodegeneration (tau-tangles, amyloid-β-plaques, phospho-Tar-DNA-Binding-Protein-43 [pTDP-43]), regardless of disease stage. One potential mechanism linking CSVD and proteinopathies is a failure in perivascular brain clearance.Acta neuropathologica communicationsRelationship between cerebral small vessel disease and proteinopathies in the medial temporal lobe.PMC12265290T32 GM144273R00AG059893K99AG080134243291van den Berg MLvan Veluw SJConnors TRotta JBax FOltmer JAuger CAAugustinack JPerbet RGreenberg SMHyman BTPerosa VFrosch MPfalseRelationship between cerebral small vessel disease and proteinopathies in the medial temporal lobe.The medial temporal lobe (MTL) is strategically important for cognition and the pathogenesis of Alzheimer's Disease (AD). Cerebral small vessel disease (CSVD) independently contributes to cognitive impairment and is believed to play a role in AD. CSVD and proteinopathies related to AD often coexist in the MTL but neither the severity of CSVD, nor the associations between these pathologies have been quantitatively addressed in this brain region. We hypothesized that the severity of CSVD in the MTL is associated with the local burden of proteinopathies implicated in neurodegeneration (tau-tangles, amyloid-β-plaques, phospho-Tar-DNA-Binding-Protein-43 [pTDP-43]), regardless of disease stage. One potential mechanism linking CSVD and proteinopathies is a failure in perivascular brain clearance.2025-01-01T00:00:00Z2025 Jul2026-03-18T13:57:14.343Z2025-08-27T03:06:55.269ZS-EPMC122652904067104710.1186/s40478-025-02076-y