Progranulin and Amyloid-β Levels: Relationship to Neuropsychology in Frontotemporal and Alzheimer's Disease

J Alzheimers Dis. 2015;46(2):375-80. doi: 10.3233/JAD-150069.

Abstract

Background: Analysis of cerebrospinal fluid (CSF) has improved over the last few years; thus specific markers for different diseases have emerged, e.g., amyloid-β (Aβ) for Alzheimer's disease (AD) and progranulin for frontotemporal dementia (FTD).

Objective: Evaluation of correlation between biomarkers in CSF and cognitive performance in populations with AD and FTD.

Methods: 27 patients with AD and 16 with FTD were included. CSF tau, P-tau(181P), Aβ₄₂, and progranulin (PGRN) were measured and a standardized neuropsychological test battery applied. Olfactory testing was additionally included where available.

Results: For all patients across both groups, an association between PGRN and categoric (p = 0.016) and letter fluency (p = 0.029), naming (p = 0.003), and overall cognition (Mini-Mental State Examination: p = 0.04) was observed. Aβ42 was strongly associated with memory function (learning: p = 0.001; recall: p = 0.002). A correlation between Aβ₄₂ and memory performance was moreover found for each group separately, while PGRN also showed a correlation with recognition memory (p = 0.04) in AD. Furthermore, an association between reduced PGRN and olfactory dysfunction was revealed (p = 0.01).

Conclusions: CSF-levels of PGRN and Aβ₄₂ levels express deficits in cognition differentially, with PGRN being predominantly associated with frontal and Aβ₄₂ with temporal dysfunction. This mirrors the cerebral occurrence of these proteins. These associations appear to be consistent across both disease groups. The relationship between PGRN and olfaction further underpins the association between PRGN and frontal dysfunction.

Keywords: Alzheimer’s disease; amyloid-beta; cerebrospinal fluid; cognitive neuropsychology in dementia; frontotemporal dementia; progranulin.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Cognition
  • Female
  • Frontotemporal Dementia / cerebrospinal fluid*
  • Frontotemporal Dementia / psychology
  • Germany
  • Humans
  • Intercellular Signaling Peptides and Proteins / cerebrospinal fluid*
  • Male
  • Memory
  • Middle Aged
  • Neuropsychological Tests
  • Peptide Fragments / cerebrospinal fluid*
  • Progranulins
  • Retrospective Studies
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Peptide Fragments
  • Progranulins
  • amyloid beta-protein (1-42)
  • tau Proteins