Cerebrospinal Fluid Alzheimer's Disease Biomarkers Across the Spectrum of Lewy Body Diseases: Results from a Large Multicenter Cohort

J Alzheimers Dis. 2016 Aug 18;54(1):287-95. doi: 10.3233/JAD-160322.

Abstract

Background: Concomitant Alzheimer's disease (AD) pathology is observed in Lewy body diseases (LBD), but the clinical impact is unknown. Only a few biomarker studies in LBD exist and have included small cohorts from single centers.

Objective: We aimed to evaluate the prevalence of abnormal cerebrospinal fluid (CSF) AD biomarkers across the spectrum of LBD in a large multicenter cohort and to assess whether an AD biomarker profile was associated with demographic and clinical differences in dementia with Lewy bodies (DLB).

Methods: We included 375 DLB patients, 164 Parkinson's disease (PD) patients without dementia, and 55 PD patients with dementia (PDD) from 10 centers. CSF amyloid-beta42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) values were dichotomized as abnormal or normal according to locally available cut-off values. A CSF AD profile was defined as abnormal Aβ42 combined with abnormal t-tau and/or p-tau.

Results: A substantial proportion of DLB patients had abnormal values for CSF Aβ42, t-tau, and p-tau, while abnormal values were uncommon in PD without dementia. Patients with PDD had values in between. A CSF AD profile was observed in 25% of DLB patients, compared with only 9% of PDD and 3% of PD without dementia. Within DLB, patients with a CSF AD profile were older, more often female, performed worse on the Mini-Mental State Examination, and had shorter disease duration compared with patients with normal CSF.

Conclusion: A CSF AD profile is more common in DLB compared with PDD and PD, and is associated with more severe cognitive impairment in DLB.

Keywords: Amyloid beta-protein (1-42); Lewy body disease; biomarkers; cerebrospinal fluid; dementia with Lewy bodies; tau protein.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Cohort Studies
  • Female
  • Humans
  • Lewy Body Disease / cerebrospinal fluid*
  • Male
  • Mental Status and Dementia Tests
  • Parkinson Disease / cerebrospinal fluid*
  • Peptide Fragments / cerebrospinal fluid*
  • Phosphorylation
  • Prevalence
  • Sex Factors
  • Time Factors
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • MAPT protein, human
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins