Rates of regional tau accumulation in ageing and across the Alzheimer's disease continuum: an AIBL
(18)F-MK6240
Alzheimer's disease
Longitudinal
Positron emission tomography (PET)
Tau
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Feb 2023
Feb 2023
Historique:
received:
26
06
2022
revised:
15
12
2022
accepted:
10
01
2023
pubmed:
30
1
2023
medline:
15
2
2023
entrez:
29
1
2023
Statut:
ppublish
Résumé
Tau positron emission tomography (PET) imaging enables longitudinal observation of tau accumulation in Alzheimer's disease (AD). One hundred and eighty-four participants: 89 cognitively unimpaired (CU) beta-amyloid negative (Aβ-), 44 CU Aβ+, 51 cognitively impaired Aβ+ (26 with mild cognitive impairment [MCI] and 25 with dementia) had follow-up CU Aβ- participants had very low rates of tau accumulation in the mesial temporal lobe (MTL). In CU Aβ+, significantly higher rate of accumulation was seen in the MTL (particularly the amygdala), extending into the inferior temporal lobes. In MCI Aβ+, the rate of accumulation was greatest in the lateral temporal, parietal and lateral occipital cortex, and plateaued in the MTL. Accumulation was global in AD Aβ+, except for a plateau in the MTL. The eroded subcortical white matter reference region showed no significant advantage over the cerebellar cortex and appeared prone to spill-over in AD participants. Data fitting suggested approximately 15-20 years to accumulate tau to typical AD levels. Tau accumulation occurs slowly. Rates vary according to brain region, disease stage and tend to plateau at high levels. Rates of tau accumulation are best measured in the MTL and inferior temporal cortex in preclinical AD and in large neocortical areas, in MCI and AD. NHMRC; Cerveau Technologies.
Sections du résumé
BACKGROUND
BACKGROUND
Tau positron emission tomography (PET) imaging enables longitudinal observation of tau accumulation in Alzheimer's disease (AD).
METHODS
METHODS
One hundred and eighty-four participants: 89 cognitively unimpaired (CU) beta-amyloid negative (Aβ-), 44 CU Aβ+, 51 cognitively impaired Aβ+ (26 with mild cognitive impairment [MCI] and 25 with dementia) had follow-up
FINDINGS
RESULTS
CU Aβ- participants had very low rates of tau accumulation in the mesial temporal lobe (MTL). In CU Aβ+, significantly higher rate of accumulation was seen in the MTL (particularly the amygdala), extending into the inferior temporal lobes. In MCI Aβ+, the rate of accumulation was greatest in the lateral temporal, parietal and lateral occipital cortex, and plateaued in the MTL. Accumulation was global in AD Aβ+, except for a plateau in the MTL. The eroded subcortical white matter reference region showed no significant advantage over the cerebellar cortex and appeared prone to spill-over in AD participants. Data fitting suggested approximately 15-20 years to accumulate tau to typical AD levels.
INTERPRETATION
CONCLUSIONS
Tau accumulation occurs slowly. Rates vary according to brain region, disease stage and tend to plateau at high levels. Rates of tau accumulation are best measured in the MTL and inferior temporal cortex in preclinical AD and in large neocortical areas, in MCI and AD.
FUNDING
BACKGROUND
NHMRC; Cerveau Technologies.
Identifiants
pubmed: 36709581
pii: S2352-3964(23)00015-4
doi: 10.1016/j.ebiom.2023.104450
pmc: PMC9900352
pii:
doi:
Substances chimiques
tau Proteins
0
Amyloid beta-Peptides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104450Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests CCR was the recipient of a research grant from Cerveau (institution), who supplied the MK6240 tau tracer precursor for research use. CCR has received consulting fees from Prothera and Merck (scientific advisory panels) and Biogen (for preparation of educational material). CCR has received support for attending meetings and/or travel from Cerveau and the Alzheimer's Association. VLV has received consulting fees from IXICO, Eli Lilly, Life molecular imaging and has received payment/honoraria from ACE Barcelona. VLV has participated on the data safety monitoring/advisory board of Eli Lilly. JF was the recipient of a research grant from the National Health and Medical Research Council (NHMRC), grant numbers APP1132604 and APP1140955. NK, VD, JR, LW, CF, PB, and CLM do not report any disclosures.