Further Understanding the Connection Between Alzheimer's Disease and Down Syndrome

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2020 Jun 17

PMID 32544310

Citations 50

Authors

Heather M Snyder

Lisa J Bain

Adam M Brickman

Maria C Carrillo

Anna J Esbensen

Joaquin M Espinosa

Fabian Fernandez

Juan Fortea

Sigan L Hartley

Elizabeth Head

James Hendrix

Priya S Kishnani

Florence Lai

Patrick Lao

Cynthia Lemere

William Mobley

Elliott J Mufson

Huntington Potter

Shahid H Zaman

Ann-Charlotte Granholm

H Diana Rosas

Andre Strydom

Michelle Sie Whitten

Michael S Rafii

Affiliations

Soon will be listed here.

Abstract

Improved medical care of individuals with Down syndrome (DS) has led to an increase in life expectancy to over the age of 60 years. In conjunction, there has been an increase in age-related co-occurring conditions including Alzheimer's disease (AD). Understanding the factors that underlie symptom and age of clinical presentation of dementia in people with DS may provide insights into the mechanisms of sporadic and DS-associated AD (DS-AD). In March 2019, the Alzheimer's Association, Global Down Syndrome Foundation and the LuMind IDSC Foundation partnered to convene a workshop to explore the state of the research on the intersection of AD and DS research; to identify research gaps and unmet needs; and to consider how best to advance the field. This article provides a summary of discussions, including noting areas of emerging science and discovery, considerations for future studies, and identifying open gaps in our understanding for future focus.

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References

Bateman R, Aisen P, De Strooper B, Fox N, Lemere C, Ringman J . Autosomal-dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease. Alzheimers Res Ther. 2011; 3(1):1. PMC: 3109410. DOI: 10.1186/alzrt59. View

Sleegers K, Brouwers N, Gijselinck I, Theuns J, Goossens D, Wauters J . APP duplication is sufficient to cause early onset Alzheimer's dementia with cerebral amyloid angiopathy. Brain. 2006; 129(Pt 11):2977-83. DOI: 10.1093/brain/awl203. View

Gordon B, Blazey T, Su Y, Hari-Raj A, Dincer A, Flores S . Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer's disease: a longitudinal study. Lancet Neurol. 2018; 17(3):241-250. PMC: 5816717. DOI: 10.1016/S1474-4422(18)30028-0. View

Godbolt A, Cipolotti L, Watt H, Fox N, Janssen J, Rossor M . The natural history of Alzheimer disease: a longitudinal presymptomatic and symptomatic study of a familial cohort. Arch Neurol. 2004; 61(11):1743-8. DOI: 10.1001/archneur.61.11.1743. View

Holth J, Patel T, Holtzman D . Sleep in Alzheimer's Disease - Beyond Amyloid. Neurobiol Sleep Circadian Rhythms. 2017; 2:4-14. PMC: 5312809. DOI: 10.1016/j.nbscr.2016.08.002. View

Wiseman F, Al-Janabi T, Hardy J, Karmiloff-Smith A, Nizetic D, Tybulewicz V . A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome. Nat Rev Neurosci. 2015; 16(9):564-74. PMC: 4678594. DOI: 10.1038/nrn3983. View

Preische O, Schultz S, Apel A, Kuhle J, Kaeser S, Barro C . Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease. Nat Med. 2019; 25(2):277-283. PMC: 6367005. DOI: 10.1038/s41591-018-0304-3. View

Sheehan R, Sinai A, Bass N, Blatchford P, Bohnen I, Bonell S . Dementia diagnostic criteria in Down syndrome. Int J Geriatr Psychiatry. 2014; 30(8):857-63. PMC: 4678599. DOI: 10.1002/gps.4228. View

Stern Y . Cognitive reserve in ageing and Alzheimer's disease. Lancet Neurol. 2012; 11(11):1006-12. PMC: 3507991. DOI: 10.1016/S1474-4422(12)70191-6. View

10.

Lewczuk P, Ermann N, Andreasson U, Schultheis C, Podhorna J, Spitzer P . Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer's disease. Alzheimers Res Ther. 2018; 10(1):71. PMC: 6064615. DOI: 10.1186/s13195-018-0404-9. View

11.

Hartley D, Blumenthal T, Carrillo M, DiPaolo G, Esralew L, Gardiner K . Down syndrome and Alzheimer's disease: Common pathways, common goals. Alzheimers Dement. 2014; 11(6):700-9. PMC: 4817997. DOI: 10.1016/j.jalz.2014.10.007. View

12.

Prasher V, Farrer M, Kessling A, Fisher E, West R, Barber P . Molecular mapping of Alzheimer-type dementia in Down's syndrome. Ann Neurol. 1998; 43(3):380-3. DOI: 10.1002/ana.410430316. View

13.

Annus T, Wilson L, Hong Y, Acosta-Cabronero J, Fryer T, Cardenas-Blanco A . The pattern of amyloid accumulation in the brains of adults with Down syndrome. Alzheimers Dement. 2015; 12(5):538-45. PMC: 4867786. DOI: 10.1016/j.jalz.2015.07.490. View

14.

Wisniewski K, Wisniewski H, Wen G . Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Ann Neurol. 1985; 17(3):278-82. DOI: 10.1002/ana.410170310. View

15.

Cataldo A, Petanceska S, Peterhoff C, Terio N, Epstein C, Villar A . App gene dosage modulates endosomal abnormalities of Alzheimer's disease in a segmental trisomy 16 mouse model of down syndrome. J Neurosci. 2003; 23(17):6788-92. PMC: 6740714. View

16.

Barnard N, Bush A, Ceccarelli A, Cooper J, de Jager C, Erickson K . Dietary and lifestyle guidelines for the prevention of Alzheimer's disease. Neurobiol Aging. 2014; 35 Suppl 2:S74-8. DOI: 10.1016/j.neurobiolaging.2014.03.033. View

17.

Torres M, Garcia O, Tang C, Busciglio J . Dendritic spine pathology and thrombospondin-1 deficits in Down syndrome. Free Radic Biol Med. 2017; 114:10-14. PMC: 7185223. DOI: 10.1016/j.freeradbiomed.2017.09.025. View

18.

Busciglio J, Pelsman A, Wong C, Pigino G, Yuan M, Mori H . Altered metabolism of the amyloid beta precursor protein is associated with mitochondrial dysfunction in Down's syndrome. Neuron. 2002; 33(5):677-88. DOI: 10.1016/s0896-6273(02)00604-9. View

19.

Zlokovic B, Yamada S, HOLTZMAN D, Ghiso J, Frangione B . Clearance of amyloid beta-peptide from brain: transport or metabolism?. Nat Med. 2000; 6(7):718-9. DOI: 10.1038/77397. View

20.

Caneus J, Granic A, Rademakers R, Dickson D, Coughlan C, Chial H . Mitotic defects lead to neuronal aneuploidy and apoptosis in frontotemporal lobar degeneration caused by MAPT mutations. Mol Biol Cell. 2017; 29(5):575-586. PMC: 6004587. DOI: 10.1091/mbc.E17-01-0031. View