Introduction
Pathophysiology of Alzheimer’s Disease in Down Syndrome
Amyloid and Related Theories
Neuroinflammation
Diagnosis of Alzheimer’s Disease in Down Syndrome
Biomarkers for the Detection of AD in DS
References | Year | Study design | Population studied | Sample | Biomarker | Method | Results |
---|---|---|---|---|---|---|---|
Tamaoka et al. [72] | 1999 | CS | 5 DS 34 HC | CSF | Aβ1-40 Aβ1-42 | NA | DS compared with control: lower Aβ1-42 |
Schupf et al. [60] | 2001 | CS | 64 nDS nAD 97 DS nAD 11 DS wAD | Plasma | Aβ1-40 Aβ1-42 | ELISA 6E10 R165 R162 | DS compared with control: higher Aβ1-40 and Aβ1-42 DS wAD compared with DS nAD: Higher Aβ1-42 |
Tapiola et al. [58] | 2001 | CS | 12 DS 19 HC | CSF | Aβ1-42 Tau | ELISA 6E10 R162 R164 hTAU | DS: Tau increased with age; Aβ1-42 decreased with age DS compared with control: lower Aβ1-42 |
Mehta et al. | 2003 | 50 DS 50 nDS | Plasma | Aβ1-40 Aβ1-42 | ELISA 6E10 R165 R226 | DS compared with control: higher Aβ1-42 in old DS | |
Schupf et al. [62] | 2007 | LF for 5 years | 207 DS | Plasma | Aβ1-40 Aβ1-42 | ELISA 6E10 R165 R162 | DS wAD compared with DS nAD: higher Aβ1-42 at baseline Elevation in plasma Aβ1-42 was associated with earlier onset of AD and increased risk of death in DS. |
Jones et al. [68] | 2009 | CS | 60 DS | Plasma | Aβ1-40 Aβ1-42 | ELISA (BioSource Intl) R226 | DS wAD compared with DS nAD: no association |
Matsuoka et al. [70] | 2009 | CS | 198 DS | Plasma | Aβ1-40 Aβ1-42 | ELISA 82E1 1A10 1C3 | Aβ1-42/ Aβ1-40 ratio was associated with presence of AD |
Schupf et al. [66] | 2010 | LF for 14–20 m | 225 DS | Plasma | Aβ1-40 Aβ1-42 | ELISA 6E10 R165 R162 | Decrease in Aβ1-42 levels, Aβ1-42/Aβ1-40 ratio, and increase in Aβ-40 levels were related to conversion to AD during follow up. Decrease in Aβ1-40 levels decreased AD risk |
Prasher et al. [67] | 2010 | LF for 6.7 years | 83 DS nAD 44 DS wAD | Plasma | Aβ1-40 Aβ1-42 | ELISA 6E10 R165 R162 | DS wAD compared with DS nAD: lower Aβ1-40. Higher Aβ1-42/Aβ1-40 ratio |
Head et al. [69] | 2010 | CS + LF | 40 DS 17 nDS wAD 52 DS wAD 26 nDS nAD | Plasma | Aβ1-40 Aβ1-42 | ELISA Wako Ltd. | DS had higher Aβ than control Aβ could not dissociate DS wAD and DS nAD |
Coppus et al. [65] | 2012 | CS + LF | 506 DS | Plasma | Aβ1-40 Aβ1-42 | xMAP Innogenetics | High Aβ1–40 and Aβ1–42 were determinants of the risk of dementia in people with DS |
Portelius et al. [73] | 2014 | CS | 12 DS 20 HC | CSF | Aβ peptide APL1β25 APL1β27 APL1β28 | MALDI TOF/TOF 6E10 4G8 ELISA APLP1 peptide | DS compared with control: decreased Aββ1-42, APL1β25, APL1β27 APL1β28; higher Aβ1-28 |
Portelius et al. [74] | 2014 | CS | 12 DS 20 HC | CSF | Aβ1-42 AβX-38/40/42 sAPPα/β T-Tau P-Tau YKL-40 CC chemokine Ligand 2 Orexin-A | Immunoassay MesoScale Discovery ELISA Innotest | DS compared with control: higher AβX-40, sAPPα, sAPPβ; lower Orexin-Α DS subject: Orexin-A decreased with age, T-tau and YKL-40 increased with age |
Rafii et al. [57] | 2015 | LF 3 years | 12 DS nAD | Plasma | AβX-38/40/42 | Immunoassay MesoScale | Greater hippocampal atrophy with amyloid load, inverse relationship between amyloid load and regional glucose metabolism Cognitive and functional measure did not correlate with amyloid load but correlated with regional FDG PET |
Dekker et al. [77] | 2015 | CS | 151 DS 22 HC | Serum | NA/A MHPG 5-HT 5-HIAA DA HVA DOPAC | RP-HPLC | DS wAD and DS converted to AD compared to DS nAD and HC: lower MHPG level |
Jenkins et al. [78] | 2016 | LF 2.9 years | 5 DS | Blood | Telomere length | PNA probe Cen2 Dako | DS wAD compared with control: shortening of telomere length over time |
Hamlett et al. [64] | 2016 | CS | DS HC | Blood | Aβ1-42 P-T181-tau P-S96-tau | ELISA | DS compared with control: higher Aβ1-42, P-T181-tau, and P-S96-tau |
Iulita et al. [76] | 2016 | LF | 31 HC 21 DS 10 DS AD | Plasma | Aβ1-38 Aβ1-40 Aβ1-42 ProNGF Neuroserpin Plasminogen MMP-1, MMP-3, MMP-9 IFN-r TNF-α IL-6 IL-8 IL-10 | ELISA 6E10 Meso-Scale Discovery | DS compared with control: higher Aβ1-40, Aβ1-42, ProNGF, MMP-1, MMP-3, MMP-9, TNF-a, IL-6 and IL-10. |
Obeid et al. [63] | 2016 | CS | 60 nDS elder 44 HC 31 DS | Plasma | Aβ1-42 SAH SAM Methylation | ELISA Innogenetics QIAGEN PSQ96 MA pyrosequencing | DS compared with control: higher SAH, Aβ1-42, lower SAM/SAH ratio and methylation % of ASPA and ITGA2B CpG sites |
Lee et al. [71] | 2017 | CS | 78 nDS 62 AD 35 DS 16 DS_D | Blood | Aβ1-40 Aβ1-42 Tau | IMR MagQu | DS compared with control: higher Aβ-40 and tau levels, lower Aβ-42 level and Aβ-42/Aβ-40 ratio DS_D compared with DS: decreased Aβ-40 and increased Aβ-42 levels and Aβ-42/40 ratios |