ArticleScientific reports2025
Exome sequencing of a Portuguese cohort of early-onset Alzheimer's disease implicates the X-linked lysosomal gene GLA.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Transcriptomic signatures in Gaucher disease subtypes: A systems biology perspective.Molecular genetics and metabolism reports · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
Cerebrovascular disease is a common comorbidity in patients with Alzheimer's disease (AD) and other dementias. Accumulating evidence suggests that dysfunction of the cerebral vasculature and AD neuropathology interact in multiple ways. Additionally, common variants in COL4A1 and rare variants in HTRA1, NOTCH3, COL4A1, and CST3 have been associated with AD pathogenesis. We aimed to search for rare genetic variants in genes associated with monogenic small vessel disease in a cohort of Portuguese early-onset AD patients. We performed whole-exome sequencing in 104 thoroughly studied patients with early-onset AD who lacked known pathogenic variants in the genes associated with AD or frontotemporal dementia. We searched for rare (minor allele frequency < 0.001) non-synonymous variants in genes associated with small vessel disease: NOTCH3, HTRA1, COL4A1, COL4A2, CSTA, GLA, and TREX1. We identified 12 rare variants in 18 patients (17.3% of the cohort). Three male AD patients carried a pathogenic GLA variant (p.Arg118Cys). One of these patients had a definite neuropathological study, confirming the diagnosis of AD and showing concomitant Fabry pathology in CA1-CA4 and the subiculum. We also found several rare variants in other genes associated with cSVD (NOTCH3, COL4A2 and HTRA1), corroborating previous studies and providing further support for the possibility that cSVD genes may play a role in AD pathogenesis. The presence of the same GLA variant in 3 early-onset AD patients, with no other genetic cause for the disease, together with the colocalization of Fabry disease pathology in areas relevant for AD pathogenesis, suggest GLA may have a role in its pathophysiology, possibly parallel to that of GBA in Parkinson's disease, meriting further studies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.