Biomarkers for early diagnosis of Alzheimer disease: ‘ALZheimer ASsociated gene’– a new blood biomarker?

Journal of Cellular and Molecular Medicine - Tập 12 Số 4 - Trang 1094-1117 - 2008
K. A. Jellinger1, Bernd Janetzky2, Johannes Attems3, Elisabeth Kienzl4
1Institute of Clinical Neurobiology, Vienna, Austria
2Neurological Clinic, Technical University, Dresden, Germany
3Department of Pathology, OWS Hospital, Vienna, Austria
4TU Biomed-Neuroscience, Technical University of Vienna, Austria

Tóm tắt

Introduction

Pathogenesis of AD

Alzheimer pathology and diagnosis

Biomarkers of AD

ALZheimer ASsociated protein (ALZAS)

Conclusions

Abstract

Simple, non‐invasive tests for an early detection of degenerative dementia by use of biomarkers are urgently required. However, up to the present, no validated extracerebral diagnostic markers (plasma/serum, platelets, urine, connective tissue) for the early diagnosis of Alzheimer disease (AD) are available. In disease stages with evident cognitive disturbances, the clinical diagnosis of probable AD is made with around 90% accuracy using modern clinical, neuropsychological and imaging methods. Diagnostic sensitivity and specificity even in early disease stages are improved by CSF markers, in particular combined tau and amyloid β peptides (Aβ) and plasma markers(e.g.Aβ‐42/Aβ‐40 ratio). Recently, a novel gene/protein – ALZAS (ALZheimer ASsociated protein) – with a 79 amino acid sequence, containing the amyloid β‐42 fragment (Aβ‐42), the amyloid precursor protein (APP) transmembrane signal and a 12 amino acid C‐terminal, not present in any other known APP alleles, has been discovered on chromosome 21 within the APP region. Reverse transcriptase‐PCR revealed the expression of the transcript of this protein in the cortex and hippocampal regions as well as in lymphocytes of human AD patients. The expression of ALZAS is mirrored by a specific autoimmune response in AD patients, directed against the ct‐12 end of the ALZAS‐peptide but not against the Aβ‐sequence. ELISA studies of plasma dectected highest titres of ALZAS in patients with mild cognitive impairment (presymptomatic AD), but only moderately increased titres in autopsy‐confirmed AD, whereas low or undetectable ct‐12 titres were found in cognitively intact age‐matched subjects and young controls. The antigen, ALZAS protein, was detected in plasma in later clinical stages of AD. It is suggested that ALZAS represents an indicator in a dynamic equilibrium between both peripheral and brain degenerative changes in AD and may become a useful ‘non‐invasive’ diagnostic markerviaa simple blood test.

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Journal of Cellular and Molecular Medicine

Tập 12 Số 4

1094-1117

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