TY  - JOUR
AU  - He, Bing
AU  - Ospina Lopera, Paula
AU  - Espinosa, Alejandro
AU  - Becerra, Juan Camilo
AU  - Osorio, Laura
AU  - Alzate, Diana
AU  - Alvarez, Sergio
AU  - Grazia, Alice
AU  - Teipel, Stefan J
AU  - Malotaux, Vincent
AU  - Tristão-Pereira, Catarina
AU  - Rowe, Meredith C
AU  - Giudicessi, Averi
AU  - Su, Yi
AU  - Chen, Yinghua
AU  - Do Carmo, Sonia
AU  - Aguillón, David
AU  - Cuello, A Claudio
AU  - Quiroz, Yakeel T
TI  - Association between basal forebrain volume and age in the presenilin-1 E280A autosomal dominant Alzheimer's disease kindred.
JO  - Alzheimer's and dementia
VL  - 22
IS  - 1
SN  - 1552-5260
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2026-00001
SP  - e71052
PY  - 2026
AB  - 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.
KW  - Humans
KW  - Presenilin-1: genetics
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: pathology
KW  - Alzheimer Disease: diagnostic imaging
KW  - Male
KW  - Female
KW  - Basal Forebrain: pathology
KW  - Basal Forebrain: diagnostic imaging
KW  - Magnetic Resonance Imaging
KW  - Middle Aged
KW  - Adult
KW  - Neuropsychological Tests
KW  - Aged
KW  - Cognitive Dysfunction: pathology
KW  - Cognitive Dysfunction: genetics
KW  - Colombia
KW  - autosomal dominant Alzheimer's disease (Other)
KW  - basal forebrain (Other)
KW  - brain volume (Other)
KW  - memory (Other)
KW  - presenilin 1 (Other)
KW  - Presenilin-1 (NLM Chemicals)
KW  - PSEN1 protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41476026
DO  - DOI:10.1002/alz.71052
UR  - https://pub.dzne.de/record/283105
ER  -