Apolipoprotein A1 in Cerebrospinal Fluid and Plasma and Progression to Alzheimer's Disease in Non-Demented Elderly

J Alzheimers Dis. 2017;56(2):687-697. doi: 10.3233/JAD-151068.


Background: HDL-cholesterol transporter Apolipoprotein A1 (ApoA1) holds neuroprotective properties, such as inhibition of amyloid-β aggregation. Low plasma ApoA1 concentrations are associated with Alzheimer's disease (AD). Little is known about ApoA1 levels in the pre-dementia stages of AD.

Objective: To investigate associations between cerebrospinal fluid (CSF) and plasma ApoA1 levels and clinical progression toward AD in non-demented elderly.

Methods: From the Amsterdam Dementia Cohort, we included 429 non-demented elderly with subjective cognitive decline (SCD; n = 206, 61±9 years, Mini-Mental State Exam (MMSE) 28±2) and mild cognitive impairment (MCI; n = 223, 67±8 years, MMSE 27±2), with a mean follow-up of 2.5±1.6 years. We used Cox proportional hazard models to investigate relations between CSF and plasma ApoA1 concentrations and clinical progression, defined as progression to MCI or AD for SCD, and progression to AD for MCI. Analyses were adjusted for age, gender, MMSE, and plasma cholesterol levels. Analyses were stratified for diagnosis and APOEɛ4 carriership.

Results: 117 patients (27%) showed clinical progression. One standard deviation increase of CSF ApoA1 was associated with a 30% increased risk of clinical progression (hazard ratio (HR) (95% CI) = 1.3(1.0-1.6)). The effect appeared to be attributable to the APOEɛ4 carriers with SCD (HR 3.3(1.0-10.9)). Lower plasma ApoA1 levels were associated with an increased risk of clinical progression in APOEɛ4 carriers with SCD (HR 5.0(1.3-18.9)).

Conclusion: Higher CSF and lower plasma ApoA1 levels were associated with an increased risk of clinical progression in APOEɛ4 carriers with SCD; suggesting that ApoA1 may be involved in the earliest stages of AD.

Keywords: Alzheimer’s disease; Apolipoprotein E; Apolipoprotein-A1; mild cognitive impairment; subjective cognitive decline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / genetics
  • Apolipoprotein A-I / blood*
  • Apolipoprotein A-I / cerebrospinal fluid*
  • Apolipoprotein E4 / genetics
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Cholesterol / blood
  • Cognitive Dysfunction / blood*
  • Cognitive Dysfunction / cerebrospinal fluid*
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / psychology
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Heterozygote
  • Humans
  • Male
  • Mental Status and Dementia Tests
  • Middle Aged
  • Neuropsychological Tests
  • Perception
  • Proportional Hazards Models
  • Risk Factors


  • APOA1 protein, human
  • Apolipoprotein A-I
  • Apolipoprotein E4
  • Biomarkers
  • Cholesterol