Alzheimer CSF biomarkers may be misleading in normal-pressure hydrocephalus

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Objective: This article discusses why CSF biomarkers found in normal-pressure hydrocephalus (NPH) can be misleading when distinguishing NPH from comorbid NPH with Alzheimer disease (AD). Methods: We describe NPH CSF biomarkers and how shunt surgery can change them. We hypothesize the effects that hydrocephalus may play on interstitial fluid space and amyloid precursor protein (APP) fragment drainage into the CSF based on a recent report and how this may explain the misleading CSF NPH biomarker findings. Results: In NPH, b-amyloid protein 42 (Aβ42) is low (as in AD), but total tau (t-tau) and phospho-tau (p-tau) levels are normal, providing conflicting biomarker findings. Low Aβ42 supports an AD diagnosis but tau findings do not. Importantly, not only Aβ42, but all APP fragments and tau proteins are low in NPH CSF. Further, these proteins increase after shunting. An increase in interstitial space and APP fragment drainage into the CSF during sleep was reported recently. Conclusions: In the setting of hydrocephalus when the brain is compressed, a decrease in interstitial space and APP protein fragment drainage into the CSF may be impeded, resulting in low levels of all APP fragments and tau proteins, which has been reported. Shunting, which decompresses the brain, would create more room for the interstitial space to increase and protein waste fragments to drain into the CSF. In fact, CSF proteins increase after shunting. CSF biomarkers in pre-shunt NPH have low Aβ42 and tau protein levels, providing misleading information to distinguish NPH from comorbid NPH plus AD.

Original languageEnglish (US)
Pages (from-to)1573-1575
Number of pages3
JournalNeurology
Volume83
Issue number17
DOIs
StatePublished - Oct 1 2014

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Normal Pressure Hydrocephalus
Biomarkers
Amyloid beta-Protein Precursor
tau Proteins
Alzheimer Disease
Drainage
Hydrocephalus
Proteins
Amyloidogenic Proteins
Extracellular Fluid
Brain
Sleep

ASJC Scopus subject areas

  • Clinical Neurology
  • Medicine(all)

Cite this

Alzheimer CSF biomarkers may be misleading in normal-pressure hydrocephalus. / Graff Radford, Neill R.

In: Neurology, Vol. 83, No. 17, 01.10.2014, p. 1573-1575.

Research output: Contribution to journalArticle

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