Prediction of Alzheimer’s Disease Using the CSF Aβ42/Aβ40 Ratio in Patients with Mild Cognitive Impairment

Abstract

Evidence supports an important role for β-amyloid (Aβ) in the pathogenesis of Alzheimer’s disease (AD). Here, we investigate baseline levels of the 40- and 42-amino-acid-long Aβ peptides (Aβ40 and Aβ42) in cerebrospinal fluid (CSF) from a cohort of patients with mild cognitive impairment (MCI, n = 137) in relation to the final diagnosis after 4–6 years of follow-up time. CSF Aβ42 concentration at baseline and the Aβ42/Aβ40 ratio were significantly decreased in the MCI patients who developed AD as compared to cognitively stable MCI patients and MCI patients who developed other forms of dementia (p < 0.001). The baseline levels of Aβ40 were similar in all MCI groups but correlated with change in Mini Mental State Examination scores in converters to AD. The Aβ42/Aβ40 ratio was superior to Aβ42 concentration with regard to identifying incipient AD in MCI (p < 0.05). In conclusion, the data provide further support for the view that amyloid precursor protein metabolism is disturbed in early sporadic AD and points to the usefulness of the Aβ42/Aβ40 ratio as a predictive biomarker for AD.

New Frontiers in Alzheimer's Disease Diagnosis

“…A consistent decrease in Aβ42 levels has been observed in the CSF of patients suffering from AD in several studies [78][79][80] but also in Subcortical White-matter Dementia (SWD) [81] and in Down Syndrome (DS) [82]. Reduced Aβ42 levels in AD are suggested to reflect either sequestration of Aβ42 in senile plaques, since Aβ42 CSF levels inversely correlate with the presence of senile plaques [83], or due to non-detectable Aβ42 oligomers in the assay, although alternative explanations may be plausible.…”

Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease

“…The SDS soluble fraction contains the most soluble A␤ whereas the formic acid (FA)-soluble fraction contains fibrillar A␤ (24). The ratio of A␤ to A␤ 1-40 is a good indication of the pathological status of an individual, and has been used as a therapeutic index (26). Consistent with previous reports, we observed a significant elevation of soluble and fibrillar A␤ and A␤ in Tg2576 mice at 8 months of age, reaching a 10-fold increase by 12-16 months of age (Fig.…”

On the early diagnosis of Alzheimer's Disease from multimodal signals: A survey

“…Aˇ40 is also present in the literature but no significant differences have been found for AD patients [63], and sometimes ratios between both Aˇ species have also been computed, suggesting that it has potential for both for distinguishing AD patients from healthy subjects and to predict AD in people suffering from MCI [60,[63][64][65]. CSF total tau, as well as some specific tau epitopes (p-tau231, p-tau181 and p-tau199), have been found to increase in AD [34,66] and some researches also affirm its predictability from MCI to AD [60,67].…”