Advances in the development of biomarkers for Alzheimer's disease: from CSF total tau and Abeta(1-42) proteins to phosphorylated tau protein.
Advances have been made to establish biological markers of Alzheimer's disease (AD). Measurement of total tau (t-tau) and beta-amyloid(1-42) (Abeta(1-42)) in the cerebrospinal fluid (CSF) seems useful to discriminate early and incipient AD from age-associated memory-impairment, depression, and some secondary dementias. New immunoassays to detect different phosphorylated tau epitopes (p-tau) have recently been developed. P-tau phosphorylated at threonine 231 (p-tau(231)) showed improvements compared to t-tau in the early detection of AD in subjects with mild cognitive impairment. As p-tau(231) declined during the course of AD, it may have potential to track disease progression. Additionally, p-tau(231) improved differential diagnosis between AD, frontotemporal dementia, and geriatric major depression. P-tau phosphorylated at threonine 181 improved diagnostic accuracy between AD and dementia with Lewy bodies. P-tau phosphorylated at serine 199 demonstrated high discriminative power between AD and non-Alzheimer's dementia. P-tau phosphorylated at serine 306/serine 404 improved differential diagnosis between AD and vascular dementia. A comparative study of the different p-tau epitopes is currently under way. In summary, first clinical multi-center studies suggest that measurement of phosphorylated tau proteins may significantly improve early and differential diagnosis and may come close to fulfilling proposed criteria of a biological marker for AD.
Hampel
Harald
H
Department of Psychiatry, Alzheimer Memorial Center and Geriatric Psychiatry Branch, Ludwig-Maximilian University, D-80336 Munich, Germany. hampel@psy.med.uni-muenchen.de
Goernitz
Alexander
A
Buerger
Katharina
K
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003704:Dementia / Q000175:diagnosis; D003863:Depression / Q000175:diagnosis; D003937:Diagnosis, Differential; D006801:Humans; D007118:Immunoassay; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins