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The pathobiology of neurovascular aging.
Neuron
January 2025
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA. Electronic address:
As global life expectancy increases, age-related brain diseases such as stroke and dementia have become leading causes of death and disability. The aging of the neurovasculature is a critical determinant of brain aging and disease risk. Neurovascular cells are particularly vulnerable to aging, which induces significant structural and functional changes in arterial, venous, and lymphatic vessels.
View Article and Find Full Text PDFCryoEM structure of an MHC-I/TAPBPR peptide-bound intermediate reveals the mechanism of antigen proofreading.
Proc Natl Acad Sci U S A
January 2025
Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
Class I major histocompatibility complex (MHC-I) proteins play a pivotal role in adaptive immunity by displaying epitopic peptides to CD8+ T cells. The chaperones tapasin and TAPBPR promote the selection of immunogenic antigens from a large pool of intracellular peptides. Interactions of chaperoned MHC-I molecules with incoming peptides are transient in nature, and as a result, the precise antigen proofreading mechanism remains elusive.
View Article and Find Full Text PDFBackground: Post-COVID cognitive dysfunctions, impacting attention, memory, and learning, might be linked to inflammation-induced blood-brain barrier (BBB) impairment. This study explores post-COVID BBB permeability changes using a non-contrast water-exchange based MRI and their associations with blood Alzheimer's biomarkers.
Method: Sixty-seven participants were classified based on COVID (COV) and cognitive (COG) statuses into three groups: COV+/COG- (n=34), COV+/COG+ (n=23), and COV- (n=10) for comparisons (COV+: Laboratory-verified SARS-CoV-2 infection; COV-: No history of SARS-CoV-2 infection and negative SARS-CoV-2 nucleocapsid antibody test.
Background: Non-invasive biofluid and MRI measures of blood-brain-barrier (BBB) dysfunction may aid early detection of cerebral small vessel disease (cSVD). Plasma markers of astrocytic function and injury, such as S100 calcium-binding protein B (S100b), have gained increased attention in relation to BBB integrity and cognition. Here we explored the inter-relationships between plasma S100b levels, an MRI measure of water exchange rate across the BBB (kw), and cognitive performance among older adults.
View Article and Find Full Text PDFBiomarkers.
Alzheimers Dement
December 2024
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Background: Biorepositories play an integral role in the advancement of our understanding of neurodegenerative diseases and improving human health outcomes. Research efforts are accelerated when access to high-quality clinical specimens is made available from a large, diverse participant group. Indiana University is home to three important neurodegenerative disease-focused biorepositories including the NIA-funded National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD), the NINDS-funded Biospecimen Exchange for Neurological Disorders (BioSEND), and the Michael J.
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