Dementia screening, biomarkers and protein misfolding: Implications for public health and diagnosis

Research output: Contribution to journalComment/debatepeer-review

20 Scopus citations

Abstract

Misfolded proteins are at the core of many neurodegenerative diseases, nearly all of them associated with cognitive impairment. For example, Creutzfeldt-Jacob disease is associated with aggregation of prion protein, 1,2 Lewy body dementia and Parkinson disease with α-synuclein 3,4 and forms of frontotemporal dementia with tau, TDP43 and a host of other proteins. 5,6 Alzheimer disease (AD), the most common cause of dementia, 7 and its prodromal syndrome mild cognitive impairment (MCI) 8 are an increasing public health problem and a diagnostic challenge to many clinicians. AD is characterized pathologically by the accumulation of amyloid β-protein (Aβ) 9,10 as senile plaques and in the walls of blood vessels as amyloid angiopathy. 11,12 Additionally, there are accumulations of tau-protein as neurofibrillary tangles and dystrophic neurites. 11,12 Biological markers of AD and MCI can serve as in vivo diagnostic indicators of underlying pathology, particularly when clinical symptoms are mild 13-15 and are likely present years before the onset of clinical symptoms. 16-19 Research to discover and refine fluid and imaging biomarkers of protein aggregation has undergone a rapid evolution 20-22 and combined analysis of different modalities may further increase diagnostic sensitivity and specificity. 23-26 Multi-center trials are now investigating whether imaging and/or cerebrospinal fluid (CSF) biomarker candidates can be used as outcome measures for use in phase III clinical trials for AD. 27-29

Original languageEnglish (US)
Pages (from-to)16-21
Number of pages6
JournalPrion
Volume5
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

Keywords

  • Alzheimer disease
  • Amyloid
  • Biomarkers
  • Dementia
  • Preclinical
  • Presymptomatic
  • Screening
  • Tau

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Infectious Diseases

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