TY  - JOUR
AU  - Kobeleva, Xenia
AU  - Rowe, Bryan
AU  - Choupan, Jeiran
AU  - Ringman, John M
AU  - Barisano, Giuseppe
AU  - Leone, Riccardo
TI  - Alterations in MRI-visible perivascular spaces precede dementia diagnosis by 18 years in autosomal dominant Alzheimer's disease.
JO  - Alzheimer's and dementia
VL  - 21
IS  - 8
SN  - 1552-5260
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2025-00966
SP  - e70588
PY  - 2025
AB  - Perivascular space (PVS) alterations are traditionally linked to cardiovascular risk factors and aging, but may also play a direct role in Alzheimer's disease (AD). To reduce confounding from age-related comorbidities, we examined PVSs in autosomal dominant AD (ADAD).In this cross-sectional study of 96 non-demented individuals (62 mutation carriers), we quantified PVS count fraction and mean diameter in white matter and basal ganglia using automated magnetic resonance imaging analysis. Linear mixed models assessed group differences along the disease course, adjusting for cardiovascular risk factors.Compared to non-carriers, mutation carriers showed lower PVS count fraction in white matter and basal ganglia, and larger PVS diameter in basal ganglia and the temporal lobe. Changes were evident up to 18 years before expected dementia onset and followed trajectories similar to amyloid beta 42 and tau biomarkers.ADAD is associated with early PVS alterations, suggesting perivascular changes may be integral to primary AD pathology.Autosomal dominant Alzheimer's disease (ADAD) mutation carriers have reduced magnetic resonance imaging-visible perivascular space (PVS) count fraction in the white matter and basal ganglia. ADAD mutation carriers show enlarged PVS in the basal ganglia and temporal white matter. PVS alterations start 18 years before the estimated time of dementia diagnosis. The spatial localization of PVS changes overlaps with regions of amyloid beta (Aβ) accumulation. The temporal evolution of PVS alterations aligns with Aβ and tau changes in the cerebrospinal fluid.
KW  - Humans
KW  - Male
KW  - Female
KW  - Magnetic Resonance Imaging
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: pathology
KW  - Alzheimer Disease: diagnostic imaging
KW  - Cross-Sectional Studies
KW  - Middle Aged
KW  - White Matter: diagnostic imaging
KW  - White Matter: pathology
KW  - Glymphatic System: diagnostic imaging
KW  - Glymphatic System: pathology
KW  - Basal Ganglia: pathology
KW  - Basal Ganglia: diagnostic imaging
KW  - Mutation: genetics
KW  - Aged
KW  - Amyloid beta-Peptides: cerebrospinal fluid
KW  - tau Proteins: cerebrospinal fluid
KW  - Disease Progression
KW  - Alzheimer's disease (Other)
KW  - autosomal dominant Alzheimer's disease (Other)
KW  - cerebral small vessel disease (Other)
KW  - dominantly inherited Alzheimer's disease (Other)
KW  - magnetic resonance imaging (Other)
KW  - perivascular spaces (Other)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40851076
C2  - pmc:PMC12375433
DO  - DOI:10.1002/alz.70588
UR  - https://pub.dzne.de/record/280782
ER  -