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@ARTICLE{He:283105,
author = {He, Bing and Ospina Lopera, Paula and Espinosa, Alejandro
and Becerra, Juan Camilo and Osorio, Laura and Alzate, Diana
and Alvarez, Sergio and Grazia, Alice and Teipel, Stefan J
and Malotaux, Vincent and Tristão-Pereira, Catarina and
Rowe, Meredith C and Giudicessi, Averi and Su, Yi and Chen,
Yinghua and Do Carmo, Sonia and Aguillón, David and Cuello,
A Claudio and Quiroz, Yakeel T},
title = {{A}ssociation between basal forebrain volume and age in the
presenilin-1 {E}280{A} autosomal dominant {A}lzheimer's
disease kindred.},
journal = {Alzheimer's and dementia},
volume = {22},
number = {1},
issn = {1552-5260},
address = {Hoboken, NJ},
publisher = {Wiley},
reportid = {DZNE-2026-00001},
pages = {e71052},
year = {2026},
abstract = {The basal forebrain (BF), a key cholinergic hub, undergoes
atrophy in Alzheimer's disease (AD), contributing to
cognitive decline. However, its age-related differences and
early vulnerability in autosomal dominant AD (ADAD) remain
unclear.We studied 158 individuals from the Colombian
Presenilin-1 (PSEN1) E280A kindred, including 80 carriers
(60 cognitively unimpaired, 20 cognitively impaired).
Participants underwent structural magnetic resonance
imaging, blood sampling, and neuropsychological testing.
Analysis of covariance and false discovery rate-corrected t
tests assessed group differences. Correlations evaluated
associations among BF volume, age, and cognitive scores.
Hamiltonian Markov chain Monte Carlo modeling estimated the
age at which BF volume diverged between carriers and
non-carriers.BF volume was comparable between cognitively
unimpaired carriers and non-carriers but declined more
rapidly in carriers, with divergence at ≈ 37.8 years, 6
years prior to the median age at onset of mild cognitive
impairment.BF volume changes precede the onset of clinical
symptoms in ADAD, supporting its potential as an early
biomarker of cholinergic degeneration and therapeutic
target.There were not basal forebrain (BF) volume
differences between PSEN1 E280A unimpaired carriers and
non-carriers. Age-related modeling revealed a faster BF
volume decline in carriers vs non-carriers. Age-related
differences first emerged at 37.8 years, about 6 years
before clinical onset. BF volume was related to age,
cognition, and plasma phosphorylated tau 217 levels. BF
changes may be early indicators of Alzheimer's
disease-related neurodegeneration.},
keywords = {Humans / Presenilin-1: genetics / Alzheimer Disease:
genetics / Alzheimer Disease: pathology / Alzheimer Disease:
diagnostic imaging / Male / Female / Basal Forebrain:
pathology / Basal Forebrain: diagnostic imaging / Magnetic
Resonance Imaging / Middle Aged / Adult / Neuropsychological
Tests / Aged / Cognitive Dysfunction: pathology / Cognitive
Dysfunction: genetics / Colombia / autosomal dominant
Alzheimer's disease (Other) / basal forebrain (Other) /
brain volume (Other) / memory (Other) / presenilin 1 (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:41476026},
doi = {10.1002/alz.71052},
url = {https://pub.dzne.de/record/283105},
}