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@ARTICLE{Grazia:276276,
author = {Grazia, Alice and Dyrba, Martin and Pomara, Nunzio and
Temp, Anna G and Grothe, Michel J and Teipel, Stefan J},
collaboration = {Initiative, Alzheimer's Prevention},
title = {{B}asal forebrain global functional connectivity is
preserved in asymptomatic presenilin-1 {E}280{A} mutation
carriers: {R}esults from the {C}olombia cohort.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {12},
number = {2},
issn = {2274-5807},
address = {Cham},
publisher = {Springer International Publishing},
reportid = {DZNE-2025-00255},
pages = {100030},
year = {2025},
abstract = {Imaging studies showed early atrophy of the cholinergic
basal forebrain in prodromal sporadic Alzheimer's disease
and reduced posterior basal forebrain functional
connectivity in amyloid positive individuals with subjective
cognitive decline. Similar investigations in familial cases
of Alzheimer's disease are still lacking.To test whether
presenilin-1 E280A mutation carriers have reduced basal
forebrain functional connectivity and whether this is linked
to amyloid pathology.This is a cross-sectional study that
analyzes baseline functional imaging data.We obtained data
from the Colombia cohort Alzheimer's Prevention Initiative
Autosomal-Dominant Alzheimer's Disease Trial.We analyzed
data from 215 asymptomatic subjects carrying the
presenilin-1 E280A mutation $[64\%$ female; 147 carriers (M
= 35 years), 68 noncarriers (M = 40 years)].We extracted
functional magnetic resonance imaging data using seed-based
connectivity analysis to examine the anterior and posterior
subdivisions of the basal forebrain. Subsequently, we
performed a Bayesian Analysis of Covariance to assess the
impact of carrier status on functional connectivity in
relation to amyloid positivity. For comparison, we also
investigated hippocampus connectivity.We found no effect of
carrier status on anterior (Bayesian Factor10 = 1.167) and
posterior basal forebrain connectivity (Bayesian Factor10 =
0.033). In carriers, we found no association of amyloid
positivity with basal forebrain connectivity.We falsified
the hypothesis of basal forebrain connectivity reduction in
preclinical mutation carriers with amyloid pathology. If
replicated, these findings may not only confirm a
discrepancy between familial and sporadic Alzheimer's
disease, but also suggest new potential targets for future
treatments.},
keywords = {Humans / Presenilin-1: genetics / Female / Colombia / Male
/ Cross-Sectional Studies / Adult / Magnetic Resonance
Imaging / Mutation / Basal Forebrain: diagnostic imaging /
Alzheimer Disease: genetics / Alzheimer Disease: diagnostic
imaging / Alzheimer Disease: physiopathology / Heterozygote
/ Cohort Studies / Middle Aged / Basal forebrain (Other) /
Bayesian analysis (Other) / Colombia cohort (Other) / PSEN1
E280A (Other) / Resting-state fMRI (Other) / Presenilin-1
(NLM Chemicals) / PSEN1 protein, human (NLM Chemicals)},
cin = {AG Teipel},
ddc = {610},
cid = {I:(DE-2719)1510100},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39863323},
doi = {10.1016/j.tjpad.2024.100030},
url = {https://pub.dzne.de/record/276276},
}