Biochemical markers in persons with preclinical familial Alzheimer disease

Abstract

Our data indicate that Abeta(42) is elevated in plasma in familial Alzheimer disease (FAD) mutation carriers (MCs) and suggests that this level may decrease with disease progression prior to the development of overt dementia. We also demonstrated that the ratio of Abeta(42) to Abeta(40) was reduced in the CSF of nondemented MCs and that elevations of t-tau and p-tau(181) are sensitive indicators of presymptomatic disease. Our finding of elevated F(2)-isoprostane levels in the CSF of preclinical FAD MCs suggests that oxidative stress occurs downstream to mismetabolism of amyloid precursor protein.

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

“…This finding is confirmed in an analysis by Ringman et al (2008) showing that mutation carriers have the full AD pattern of CSF biomarker changes long before symptom onset [84]. Bateman et al (2012) have also suggested that CSF Ab 1-42 may start to decrease already 25 years before the estimated clinical onset in familial AD mutation carriers, whereas increased CSF tau may be observed 15 years before predicted symptom onset [85].…”

“…Altogether, these results suggest that CSF biomarkers, especially Ab 1-42 , convert to positive several years before the first appearance of clinical signs, also in the familial form of the disease. Notably, familial AD mutation carriers -in their early 20s -may commence at higher CSF Ab 1-42 concentrations than non-mutation carriers [84,86]. It should be noted that most of the studies published to date are ''pseudo-longitudinal'' in their design; they relate crosssectional biomarker data to longitudinal clinical or neuroimaging markers or time before expected disease onset.…”

Tau oligomers in cerebrospinal fluid in Alzheimer's disease

“…MMSE scores are available for all patients. CASI scores are available for the presymptomatic patients (UCLA samples) 24. Prior to analyses, CSF samples were thawed on ice.…”

Vascular pathology to vascular dementia is it multifactorial or due to still unknown factors?

“…Postmortem studies indicate that 15% to 34% of dementia patients show significant vascular pathology, either alone or in combination with Alzheimer disease (AD) pathology suggesting substantial overlap between AD and vascular dementia [12]. Vascular amyloid angiopathy is the most common vascular lesion reported in AD.…”