Longitudinal amyloid and tau accumulation in autosomal dominant Alzheimer's disease: findings from the Colombia-Boston (COLBOS) biomarker study.
Alzheimer’s
Amyloid
Autosomal-Dominant
Imaging
Longitudinal
Tau
Journal
Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643
Informations de publication
Date de publication:
15 01 2021
15 01 2021
Historique:
received:
05
10
2020
accepted:
26
12
2020
entrez:
16
1
2021
pubmed:
17
1
2021
medline:
25
6
2021
Statut:
epublish
Résumé
Neuroimaging studies of autosomal dominant Alzheimer's disease (ADAD) enable characterization of the trajectories of cerebral amyloid-β (Aβ) and tau accumulation in the decades prior to clinical symptom onset. Longitudinal rates of regional tau accumulation measured with positron emission tomography (PET) and their relationship with other biomarker and cognitive changes remain to be fully characterized in ADAD. Fourteen ADAD mutation carriers (Presenilin-1 E280A) and 15 age-matched non-carriers from the Colombian kindred underwent 2-3 sessions of Aβ (11C-Pittsburgh compound B) and tau (18F-flortaucipir) PET, structural magnetic resonance imaging, and neuropsychological evaluation over a 2-4-year follow-up period. Annualized rates of change for imaging and cognitive variables were compared between carriers and non-carriers, and relationships among baseline measurements and rates of change were assessed within carriers. Longitudinal measurements were consistent with a sequence of ADAD-related changes beginning with Aβ accumulation (16 years prior to expected symptom onset, EYO), followed by entorhinal cortex (EC) tau (9 EYO), neocortical tau (6 EYO), hippocampal atrophy (6 EYO), and cognitive decline (4 EYO). Rates of tau accumulation among carriers were most rapid in parietal neocortex (~ 9%/year). EC tau PET signal at baseline was a significant predictor of subsequent neocortical tau accumulation and cognitive decline within carriers. Our results are consistent with the sequence of biological changes in ADAD implied by cross-sectional studies and highlight the importance of EC tau as an early biomarker and a potential link between Aβ burden and neocortical tau accumulation in ADAD.
Sections du résumé
BACKGROUND
Neuroimaging studies of autosomal dominant Alzheimer's disease (ADAD) enable characterization of the trajectories of cerebral amyloid-β (Aβ) and tau accumulation in the decades prior to clinical symptom onset. Longitudinal rates of regional tau accumulation measured with positron emission tomography (PET) and their relationship with other biomarker and cognitive changes remain to be fully characterized in ADAD.
METHODS
Fourteen ADAD mutation carriers (Presenilin-1 E280A) and 15 age-matched non-carriers from the Colombian kindred underwent 2-3 sessions of Aβ (11C-Pittsburgh compound B) and tau (18F-flortaucipir) PET, structural magnetic resonance imaging, and neuropsychological evaluation over a 2-4-year follow-up period. Annualized rates of change for imaging and cognitive variables were compared between carriers and non-carriers, and relationships among baseline measurements and rates of change were assessed within carriers.
RESULTS
Longitudinal measurements were consistent with a sequence of ADAD-related changes beginning with Aβ accumulation (16 years prior to expected symptom onset, EYO), followed by entorhinal cortex (EC) tau (9 EYO), neocortical tau (6 EYO), hippocampal atrophy (6 EYO), and cognitive decline (4 EYO). Rates of tau accumulation among carriers were most rapid in parietal neocortex (~ 9%/year). EC tau PET signal at baseline was a significant predictor of subsequent neocortical tau accumulation and cognitive decline within carriers.
CONCLUSIONS
Our results are consistent with the sequence of biological changes in ADAD implied by cross-sectional studies and highlight the importance of EC tau as an early biomarker and a potential link between Aβ burden and neocortical tau accumulation in ADAD.
Identifiants
pubmed: 33451357
doi: 10.1186/s13195-020-00765-5
pii: 10.1186/s13195-020-00765-5
pmc: PMC7811244
doi:
Substances chimiques
Amyloid beta-Peptides
0
Biomarkers
0
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
27Subventions
Organisme : NIA NIH HHS
ID : R01 AG031581
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG054671
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG027435
Pays : United States
Organisme : NIH HHS
ID : DP5 OD019833
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG046396
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG062559
Pays : United States
Organisme : NIA NIH HHS
ID : K23 AG058805
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062421
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG036694
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG010483
Pays : United States
Organisme : NIA NIH HHS
ID : F31 AG062158
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005134
Pays : United States
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