Plasma β‐amyloid and duration of Alzheimer's disease in adults with Down syndrome

Abstract

Objective To investigate the relation of plasma levels of Aβ peptides (Aβ1-40 and Aβ1-42) and Apolipoprotein E (APOE) genotype to dementia status and duration of Alzheimer’s disease in adults with Down syndrome (DS). Methods Adults with DS were recruited from community settings and followed up for a mean period of 6.7 years. Plasma levels Aβ1-40 and Aβ1-42 and APOE genotype were determined at the last visit. Results There were 83 nondemented participants and 44 participants with prevalent AD. Overall, plasma levels of Aβ1-42, Aβ1-40 and the ratio Aβ1-42/Aβ1-40 did not differ significantly between the adults with DS. Among demented participants the mean level of Aβ1-40 was significantly lower (157.0 vs. 195.3) and the ratio of Aβ1-42/Aβ1-40 was significantly higher (0.28 vs. 0.16) in those with more than 4 years duration of dementia than in those with 4 or fewer years duration of dementia. This pattern was generally similar in those with and without an APOE ε4 allele. Conclusions There is an association between plasma Aβ peptide levels and duration of AD in older persons with DS. The predictive and diagnostic roles of Aβ1-42 and Aβ1-40 measurements for AD, however, remain controversial. Change in Aβ peptide levels with onset of AD and with duration of dementia may account for lack of difference between prevalent cases and nondemented individuals and for variation in the predictive power of Aβ peptide levels.e

Aging in Down Syndrome and the Development of Alzheimer's Disease Neuropathology

“…In cross sectional studies comparing demented adults with DS to those without dementia, most studies report no differences in plasma Aβ1-40 [101, 104, 106, 110, 111] except in one study [112]. However, increased plasma Aβ 1-42 can distinguish demented adults with DS [104] and may improve predictive models for dementia when included [106].…”

Homozygous carriers of APP A713T mutation in an autosomal dominant Alzheimer disease family

“…27 These observations are consistent with findings published in other longitudinal studies, suggesting that plasma levels of Ab peptides increase in the preclinical phase of AD, successively declining with the progression of clinical dementia, reflecting the deposition of Ab peptides in the brain. [28][29][30][31][32][33] No substantial differences concerning clinical phenotype and course were evidenced comparing heterozygous and homozygous patients (table e-2). In these affected persons, homozygosity for the APP A713T mutation does not aggravate the clinical picture of the disease, which is in line with the classic definition of dominance.…”

Exosomal biomarkers in Down syndrome and Alzheimer's disease

“…By the age of forty, amyloid plaques and NFTs are present in the brain of persons with DS in sufficient numbers to allow a post mortem pathological diagnosis of AD (Head et al 2001; Stoltzner et al 2000; Wisniewski et al 1985; Prasher et al 2010), even though the pathological trajectory toward DS-AD is established much earlier. Beta amyloid pathology has been detected in post mortem brain samples from people with DS as young as 15 years of age (Lemere et al 1996).…”

“…The term “biomarker” refers to objective indications of a medical state that can be measured in a reproducible manner. Cerebrospinal fluid (CSF) biomarkers of AD include the Aβ peptides, Aβ 1-40 and Aβ 1-42 , different species of P-Tau, pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β, and pro-NGF, which have been detected decades prior to dementia onset in both the general population (Bayer-Carter et al 2011; Counts et al 2017; Jack et al 2012;) and in people with DS (Perluigi et al 2014; Prasher et al 2010). However, the use of CSF biomarkers is not always practical due to its invasiveness and potential risks for post-lumbar puncture (LP) headaches.…”