NPJ Dement. 2025;1(1):31. doi: 10.1038/s44400-025-00036-w. Epub 2025 Oct 10.
ABSTRACT
Early-onset Alzheimer's disease (EOAD) is a rare form of dementia that often progresses more quickly than late-onset cases, and is more commonly associated with autosomal dominant mutations. A 47-year-old male presented with progressive cognitive and behavioral decline, a family history of EOAD, and was later found to have a novel pathogenic PSEN1 variant (c.519 G > T, p.Leu173Phe). Initial evaluations, including neuroimaging and laboratory tests, were unremarkable. Neuropsychological testing later revealed memory impairment, executive dysfunction, and neuropsychiatric symptoms. These features, alongside the identified mutation, are consistent with phenotypic presentations of EOAD involving the third transmembrane domain of PSEN1. Pharmacological treatment with cholinesterase inhibitors and antipsychotics yielded limited benefit. Notably, the extended follow-up time, of more than 10 years from the early symptomatic stage, is a unique and valuable feature of this case study, providing rare longitudinal insight into the natural course of genetically confirmed EOAD.
PMID:41078387 | PMC:PMC12513822 | DOI:10.1038/s44400-025-00036-w
Authors
Lina Zapata, MD
Psychiatrist
Bruce Miller, MD
Founding Director, University of California, San Francisco
Kate Possin, PhD
Professor of Neurology
Victor Valcour, MD, PhD
Site Director, University of California, San Francisco
Stefanie Piña Escudero, MD
Geriatrician
Agustín Ibáñez, PhD
Neuroscientist
