Characterizing the emergence of amyloid and tau burden in Down syndrome.

Autor: Zammit MD; University of Wisconsin-Madison Waisman Center, Madison, Wisconsin, USA., Betthauser TJ; University of Wisconsin-Madison Alzheimer's Disease Research Center, Madison, Wisconsin, USA.; Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., McVea AK; University of Wisconsin-Madison Waisman Center, Madison, Wisconsin, USA., Laymon CM; Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Tudorascu DL; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Johnson SC; University of Wisconsin-Madison Alzheimer's Disease Research Center, Madison, Wisconsin, USA.; Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., Hartley SL; University of Wisconsin-Madison Waisman Center, Madison, Wisconsin, USA., Converse AK; University of Wisconsin-Madison Waisman Center, Madison, Wisconsin, USA., Minhas DS; Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Zaman SH; Cambridge Intellectual Disability Research Group, University of Cambridge, Cambridge, UK., Ances BM; Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA., Stone CK; Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., Mathis CA; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Cohen AD; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Klunk WE; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Handen BL; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Christian BT; University of Wisconsin-Madison Waisman Center, Madison, Wisconsin, USA.; Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2024 Jan; Vol. 20 (1), pp. 388-398. Date of Electronic Publication: 2023 Aug 29.
DOI: 10.1002/alz.13444
Abstrakt: Introduction: Almost all individuals with Down syndrome (DS) will develop neuropathological features of Alzheimer's disease (AD). Understanding AD biomarker trajectories is necessary for DS-specific clinical interventions and interpretation of drug-related changes in the disease trajectory.
Methods: A total of 177 adults with DS from the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) underwent positron emission tomography (PET) and MR imaging. Amyloid-beta (Aβ) trajectories were modeled to provide individual-level estimates of Aβ-positive (A+) chronicity, which were compared against longitudinal tau change.
Results: Elevated tau was observed in all NFT regions following A+ and longitudinal tau increased with respect to A+ chronicity. Tau increases in NFT regions I-III was observed 0-2.5 years following A+. Nearly all A+ individuals had tau increases in the medial temporal lobe.
Discussion: These findings highlight the rapid accumulation of amyloid and early onset of tau relative to amyloid in DS and provide a strategy for temporally characterizing AD neuropathology progression that is specific to the DS population and independent of chronological age.
Highlights: Longitudinal amyloid trajectories reveal rapid Aβ accumulation in Down syndrome NFT stage tau was strongly associated with A+ chronicity Early longitudinal tau increases were observed 2.5-5 years after reaching A.
(© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE
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