Clinical heterogeneity in mild cognitive impairment - Beyond clinical diagnosis-towards imaging amyloid

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Abstract

Alzheimer's disease (AD) generally begins with mild memory problems in an insidious manner and progresses to develop multiple cognitive and functional impairment within a few years. Currently, the diagnosis of AD requires multiple cognitive deficits including memory disturbance and exclusion of other dementing disorders. However, normal elderly people quite commonly complain of increasing forgetfulness with age, and we have not developed an objective tool that can reliably support the diagnosis of AD. Recent advances in our understanding of neurobiology of AD demonstrate that AD starts with accumulation of amyloid β-protein (Aβ) followed by abnormal phosphorylation of tau protein and a massive neuron death in vulnerable brain areas. We have shown that cerebrospinal fluid tau are elevated in subjects with mild cognitive impairment (MCI), the earliest detectable clinical stage of dementia and AD, suggesting that the pathogenic cascade of AD may arrive at the stage that finally leads to an accumulation of abnormally phosphorylated tau in the MCI stage. These results may highlight the need to develop another diagnostic tool that reliably monitors and visualize brain β-amyloid burden in living subjects who are at increased risk of developing AD. We assume that the detection of asymptomatic stage of AD followed by an early intervention may lead to maximum therapeutic benefits. In an attempt to accomplish this goal, we have generated several novel chemicals that specifically bind to Aβ peptide upon entry into rat brain. The "amyloid imaging" seems quite promising if safely and successfully applied in humans because it is a non-invasive technique and applied multiple times in a single subject.

Original languageEnglish
Pages (from-to)924-928
Number of pages5
JournalClinical Neurology
Volume44
Issue number11
Publication statusPublished - 2004 Nov 1

Keywords

  • Cerebrospinal fluid tau
  • Dementia
  • Early diagnosis
  • Mild cognitive impairment
  • Periventricular white matter lesions

ASJC Scopus subject areas

  • Clinical Neurology

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