Transient focal neurological episodes (TFNE), often associated with convexity subarachnoid hemorrhage (cSAH), are common in cerebral amyloid angiopathy (CAA), but their pathophysiology remains incompletely understood. In six patients with unremitting TFNE, using high-resolution post-contrast magnetic resonance imaging and vessel wall imaging (VWI), we found various combinations of transient leptomeningeal, parenchymal and vessel wall enhancement; in 5 of 6 the enhancement included regions corresponding anatomically to symptoms. Three patients had resolution of TFNE and enhancement (2 with corticosteroid treatment, 1 without). Our observations suggest that inflammation might contribute to the pathophysiology of CAA-related TFNE and cSAH, with potential wider relevance for the associated high risks of recurrent ICH in CAA more generally. ANN NEUROL 2025.
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Background: The autophagy lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are key proteostasis mechanisms in cells, which are dysfunctional in AD and linked to protein aggregation and neuronal death. Autophagy is over activated in Alzheimer's disease brain whereas UPS is severely impaired. Activating autophagy has received most attention, however recent evidence suggests that UPS can clear aggregate proteins and a potential therapeutic target for AD and protein misfolding diseases.
View Article and Find Full Text PDFBackground: Availability of amyloid modifying therapies will dramatically increase the need for disclosure of Alzheimer's disease (AD) related genetic and/or biomarker test results. The 21st Century Cares Act requires the immediate return of most medical test results, including AD biomarkers. A shortage of genetic counselors and dementia specialists already exists, thus driving the need for scalable methods to responsibly communicate test results.
View Article and Find Full Text PDFBackground: CT1812 is an experimental therapeutic sigma-2 receptor modulator in development for Alzheimer's disease (AD) and dementia with Lewy bodies. CT1812 reduces the affinity of Aβ oligomers to bind to neurons and exert synaptotoxic effects. This phase 2, multi-center, international, randomized, double-blind, placebo-controlled trial assessed safety, tolerability and effects of CT1812 on cognitive function in individuals with AD.
View Article and Find Full Text PDFBackground: Immunotherapy of Alzheimer's disease (AD) is a promising approach to reducing the accumulation of beta-amyloid, a critical event in the onset of the disease. Targeting the group II metabotropic glutamate receptors, mGluR2 and mGluR3, could be important in controlling Aβ production, although their respective contribution remains unclear due to the lack of selective tools.
Method: 5xFAD mice were chronically treated by a brain penetrant camelid single domain antibody (VHH or nanobody) that is an activator of mGluR2.
Background: Focused ultrasound (FUS)-induced blood-brain barrier opening (BBBO) is a technique for safely, non-invasively, and transiently opening the blood brain barrier in a targeted area of the brain. Pre-clinical and clinical studies have shown that FUS is capable of decreasing amyloid plaque load and stimulating neurogenesis in Alzheimer's Disease (AD) models, in addition to being safe for use in human patients. However, the effect of FUS-BBBO on neurons has not yet been characterized, despite its crucial role in cognition and regulating brain function.
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