Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the notch3 epidermal growth factor-like repeats. A Colombian kindred carries a novel C455R mutation located in the predicted ligand-binding domain. Stroke occurred in the patients at an unusually early age (median age: 31 years) in comparison to the more frequent onset in the fourth decade of life in other CADASIL populations, including a second Colombian kindred with an R1031C mutation.
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http://dx.doi.org/10.1212/wnl.59.2.277 | DOI Listing |
J Clin Invest
October 2024
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
J Alzheimers Dis
September 2024
Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
Background: The largest identified kindred worldwide with a single mutation causing autosomal-dominant Alzheimer's disease (ADAD) is a family from Antioquia, Colombia, carrying the Presenilin-1 (PSEN1) E280A (Paisa) mutation. The majority of mutation carriers develop dementia, typically commencing in their late 30 s, with a median onset age of 49 years. Cognitive decline is a hallmark feature.
View Article and Find Full Text PDFSci Rep
May 2024
Geriatric Psychiatry Division, Nathan Kline Institute/Department of Psychiatry and Pathology, NYU Grossman School of Medicine, Orangeburg, NY, USA.
We aimed to study atrophy and glucose metabolism of the cholinergic basal forebrain in non-demented mutation carriers for autosomal dominant Alzheimer's disease (ADAD). We determined the level of evidence for or against atrophy and impaired metabolism of the basal forebrain in 167 non-demented carriers of the Colombian PSEN1 E280A mutation and 75 age- and sex-matched non-mutation carriers of the same kindred using a Bayesian analysis framework. We analyzed baseline MRI, amyloid PET, and FDG-PET scans of the Alzheimer's Prevention Initiative ADAD Colombia Trial.
View Article and Find Full Text PDFmedRxiv
August 2023
Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, 10515 W Santa Fe Drive, Sun City, AZ 85351.
Autopsy studies have demonstrated that comorbid neurodegenerative and cerebrovascular disease occur in the great majority of subjects with Alzheimer disease dementia (ADD), and are likely to additively alter the rate of decline or severity of cognitive impairment. The most important of these are Lewy body disease (LBD), TDP-43 proteinopathy and cerebrovascular disease, including white matter rarefaction (WMR) and cerebral infarcts. Comorbidities may interfere with ADD therapeutic trials evaluation of ADD clinical trials as they may not respond to AD-specific molecular therapeutics.
View Article and Find Full Text PDFAlzheimers Dement
September 2023
Neuroscience Research Institute, University of California, Santa Barbara, California, and Department of Molecular Cellular and Developmental Biology University of California, Santa Barbara, California, USA.
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