Total and phosphorylated tau proteins: Evaluation as core biomarker candidates in frontotemporal dementia

An ever increasing number of patients with neurodegenerative
disorders calls for the evaluation of potential diagnostic markers
that allow an early diagnosis and an early initiation of specific
therapy. Clinical diagnosis of Alzheimer's disease (AD), the most
common neurodegenerative disorder, reaches 80-90% accuracy upon
autopsy in specialized clinical centers. Diagnosis of AD in early
clinical or preclinical stages is far less accurate, as is the
differential diagnosis between AD and other primary dementias, such
as frontotemporal dementia (FTD). Microtubule-associated tau
protein is abnormally phosphorylated in AD and aggregates as paired
helical filaments in neurofibrillary tangles. Recently,
immunoassays have been developed detecting tau phosphorylated at
specific epitopes in cerebrospinal fluid (CSF). Four years of
clinical research consistently demonstrate that CSF phosphorylated
tau (p-tau) is highly increased in AD compared to healthy controls
and may differentiate AD from its most relevant differential
diagnoses. Tau phosphorylated at threonine 231 (p-tau(231)) shows
excellent differentiation between AD and FTD, whereas serine 181
(p-tau(181)) enhances accurate differentiation between AD and
dementia with Lewy bodies. Moreover, p-tau(231) levels decline with
disease progression, correlating with cognitive performance at
baseline. Total tau (t-tau) is regarded as a general marker of
neurodegeneration for evaluation in future population-based
studies. p-tau(231) and p-tau(181) yield excellent discrimination
between AD and non-AD dementias including FTD, exceeding the
differential diagnostic and prognostic accuracy of t-tau.
Therefore, p-tau is a core biological marker candidate for future
evaluation in large national and international multicenter
networks. Copyright (C) 2004 S. Karger AG, Basel.