Diagnosis of neurodegenerative dementia: where do we stand, now?

Abstract

After many years of large efforts made for understanding the pathogenesis of dementias, the early diagnosis of these degenerative diseases remains an open challenge. Alzheimer's disease (AD) represents the most common form of dementia, followed by Lewy body disease and frontotemporal degeneration. Actually, different pathological processes can determine similar and overlapping clinical syndrome. To detect in vivo the pathological process underlying progressive cognitive and behavior impairment, the Internationals guidelines recommend the use of biological and topographical markers, which can reflect neuropathological modifications in brain. In cerebrospinal fluid (CSF), decrease of amyloid beta 1-42 (Aβ42) and a low ratio of Aβ42 with amyloid beta 1-40 (Aβ42/Aβ40), together with the increase of both total tau protein (t-tau) and phosphorylated tau (p-tau), contribute to define the "Alzheimer's signature". This review points out on the evolution of the concept for early diagnosis of AD, and on the current use of CSF proteins for research purposes and in clinical setting. Then, we discuss the limitations and drawbacks in wide application of CSF biomarkers for diagnosing degenerative dementias, and on the role of laboratory medicine to convey these biomarkers from "research" toward "clinical practice".