Amyloid- β and tau deposition influences cognitive and functional decline in Down syndrome

Monika Grigorova; Elijah Mak; Stephanie S G Brown; Jessica Beresford-Webb; Young T Hong; Tim D Fryer; Jonathan P Coles; Franklin I Aigbirhio; Dana Tudorascu; Annie Cohen; Bradley T Christian; Beau Ances; Benjamin L Handen; Charles M Laymon; William E Klunk; Isabel C H Clare; Anthony J Holland; Shahid H Zaman

doi:10.1016/j.neurobiolaging.2022.07.003

Amyloid- β and tau deposition influences cognitive and functional decline in Down syndrome

Neurobiol Aging. 2022 Nov:119:36-45. doi: 10.1016/j.neurobiolaging.2022.07.003. Epub 2022 Jul 21.

Authors

Monika Grigorova¹, Elijah Mak², Stephanie S G Brown², Jessica Beresford-Webb², Young T Hong³, Tim D Fryer³, Jonathan P Coles⁴, Franklin I Aigbirhio³, Dana Tudorascu⁵, Annie Cohen⁵, Bradley T Christian⁶, Beau Ances⁷, Benjamin L Handen⁵, Charles M Laymon⁸, William E Klunk⁵, Isabel C H Clare², Anthony J Holland², Shahid H Zaman²

Affiliations

¹ Cambridge Intellectual and Developmental Disabilities Research Group, Department of Psychiatry, University of Cambridge, Cambridge, UK. Electronic address: CIDDRG@medschl.cam.ac.uk.
² Cambridge Intellectual and Developmental Disabilities Research Group, Department of Psychiatry, University of Cambridge, Cambridge, UK.
³ Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
⁴ Department of Medicine, University of Cambridge, Cambridge, UK.
⁵ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
⁶ Waisman Brain Imaging Laboratory, University of Wisconsin-Madison, Madison, WI, USA.
⁷ Department of Neurology, Washington University at St. Louis, St. Louis, WA, USA.
⁸ Department of Radiology and Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.

PMID: 35964542
PMCID: PMC10363400
DOI: 10.1016/j.neurobiolaging.2022.07.003

Abstract

This study investigates whether tau has (i) an independent effect from amyloid-β on changes in cognitive and functional performance and (ii) a synergistic relationship with amyloid-β in the exacerbation of decline in aging Down syndrome (DS). 105 participants with DS underwent baseline PET [¹⁸F]-AV1451 and PET [¹¹C]PiB scans to quantify tau deposition in Braak regions II-VI and the Striatum and amyloid-β status respectively. Linear Mixed Effects models were implemented to assess how tau and amyloid-β deposition are related to change over three time points. Tau was a significant independent predictor of cognitive and functional change. The three-way interaction between time, [¹¹C]PiB status and tau was significant in the models of episodic memory and visuospatial cognition. Baseline tau is a significant predictor of cognitive and functional decline, over and above the effect of amyloid-β status. Results suggest a synergistic relationship between amyloid-β status and tau as predictors of change in memory and visuospatial cognition.

Keywords: Alzheimer's disease; Amyloid-β; Down syndrome; PET [(11)C]PiB; PET [(18)F]-AV1451; Tau.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Amyloid beta-Peptides* / metabolism
Brain / metabolism
Cognition / physiology
Cognitive Aging / physiology
Cognitive Dysfunction* / metabolism
Cognitive Dysfunction* / psychology
Down Syndrome* / diagnostic imaging
Down Syndrome* / metabolism
Down Syndrome* / psychology
Humans
Positron-Emission Tomography / methods
tau Proteins* / metabolism

Substances

Amyloid beta-Peptides
MAPT protein, human
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding