CSF biomarker associations with change in hippocampal volume and precuneus thickness: Implications for the Alzheimer's pathological cascade

Nikki H. Stricker, Hiroko Dodge, N. Maritza Dowling, S. Duke Han, Elena A. Erosheva, William J. Jagust

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Neurofibrillary tangles (NFT) and amyloid plaques are hallmark neuropathological features of Alzheimer's disease (AD). There is some debate as to which neuropathological feature comes first in the disease process, with early autopsy studies suggesting that NFT develop first, and more recent neuroimaging studies supporting the early role of amyloid beta (Aβ) deposition. Cerebrospinal fluid (CSF) biomarkers of Aβ42 and hyperphosphorylated tau (p-tau) have been shown to serve as in vivo proxy measures of amyloid plaques and NFT, respectively. The aim of this study was to examine the association between CSF biomarkers and rate of atrophy in the precuneus and hippocampus. These regions were selected because the precuneus appears to be affected early and severely by Aβ deposition, and the hippocampus similarly by NFT pathology. We predicted (1) baseline Aβ42 would be related to accelerated rate of cortical thinning in the precuneus and volume loss in the hippocampus, with the latter relationship expected to be weaker, (2) baseline p-tau181p would be related to accelerated rate of hippocampal atrophy and cortical thinning in the precuneus, with the latter relationship expected to be weaker. Using all ADNI cohorts, we fitted separate linear mixed-effects models for changes in hippocampus and precuneus longitudinal outcome measures with baseline CSF biomarkers modeled as predictors. Results partially supported our hypotheses: Both baseline p-tau181p and Aβ42 were associated with hippocampal atrophy over time. Neither p-tau181p nor Aβ42 were significantly related to cortical thinning in the precuneus over time. However, follow-up analyses demonstrated that having abnormal levels of both Aβ42 and p-tau181p was associated with an accelerated rate of atrophy in both the hippocampus and precuneus. Results support early effects of Aβ in the Alzheimer's disease process, which are less apparent than and perhaps dependent on p-tau effects as the disease progresses. However, amyloid deposition alone may be insufficient for emergence of significant morphometric changes and clinical symptoms.

Original languageEnglish (US)
Pages (from-to)599-609
Number of pages11
JournalBrain Imaging and Behavior
Volume6
Issue number4
DOIs
StatePublished - 2012

Fingerprint

Parietal Lobe
Cerebrospinal Fluid
Biomarkers
Neurofibrillary Tangles
Hippocampus
Atrophy
Amyloid Plaques
Amyloid
Alzheimer Disease
Proxy
Neuroimaging
Autopsy
Outcome Assessment (Health Care)
Pathology

Keywords

  • Alzheimer's disease
  • Beta amyloid
  • Biomarkers
  • Hippocampus
  • MRI
  • Phosphorylated tau
  • Precuneus

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience
  • Behavioral Neuroscience
  • Radiology Nuclear Medicine and imaging

Cite this

CSF biomarker associations with change in hippocampal volume and precuneus thickness : Implications for the Alzheimer's pathological cascade. / Stricker, Nikki H.; Dodge, Hiroko; Dowling, N. Maritza; Han, S. Duke; Erosheva, Elena A.; Jagust, William J.

In: Brain Imaging and Behavior, Vol. 6, No. 4, 2012, p. 599-609.

Research output: Contribution to journalArticle

Stricker, Nikki H. ; Dodge, Hiroko ; Dowling, N. Maritza ; Han, S. Duke ; Erosheva, Elena A. ; Jagust, William J. / CSF biomarker associations with change in hippocampal volume and precuneus thickness : Implications for the Alzheimer's pathological cascade. In: Brain Imaging and Behavior. 2012 ; Vol. 6, No. 4. pp. 599-609.
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