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CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings.
Neurology 2012; 78(20):1568-75Neur

Abstract

OBJECTIVE

To assess the relationship between Alzheimer disease (AD)-related pathologic changes in frontal cortical brain biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships of AD biomarkers in CSF and cortical biopsy with the final clinical diagnosis of AD.

METHODS

In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), Aβ plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF Aβ42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia.

RESULTS

The patients with Aβ plaques in the cortical biopsy had lower (p = 0.009) CSF Aβ42 levels than those with no Aβ plaques. The patients with tau in the cortical biopsy had lower (p = 0.014) Aβ42 but higher (p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical biopsy. The patients with amyloid + tau + biopsies had the lowest Aβ42 and highest tau and p-tau 181 levels in CSF. The Aβ42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical Aβ was independently predicted by the APOE ε4 carrier status and age but not by CSF Aβ42 or tau levels.

CONCLUSIONS

Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF Aβ42 and high CSF tau and p-tau levels, respectively.

Authors+Show Affiliations

Unit of Neurology, Institute of Clinical Medicine, University of Eastern Finland. toni.seppala@fimnet.fiNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22517093

Citation

Seppälä, T T., et al. "CSF Biomarkers for Alzheimer Disease Correlate With Cortical Brain Biopsy Findings." Neurology, vol. 78, no. 20, 2012, pp. 1568-75.
Seppälä TT, Nerg O, Koivisto AM, et al. CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings. Neurology. 2012;78(20):1568-75.
Seppälä, T. T., Nerg, O., Koivisto, A. M., Rummukainen, J., Puli, L., Zetterberg, H., ... Herukka, S. K. (2012). CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings. Neurology, 78(20), pp. 1568-75. doi:10.1212/WNL.0b013e3182563bd0.
Seppälä TT, et al. CSF Biomarkers for Alzheimer Disease Correlate With Cortical Brain Biopsy Findings. Neurology. 2012 May 15;78(20):1568-75. PubMed PMID: 22517093.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings. AU - Seppälä,T T, AU - Nerg,O, AU - Koivisto,A M, AU - Rummukainen,J, AU - Puli,L, AU - Zetterberg,H, AU - Pyykkö,O T, AU - Helisalmi,S, AU - Alafuzoff,I, AU - Hiltunen,M, AU - Jääskeläinen,J E, AU - Rinne,J, AU - Soininen,H, AU - Leinonen,V, AU - Herukka,S K, Y1 - 2012/04/18/ PY - 2012/4/21/entrez PY - 2012/4/21/pubmed PY - 2012/7/10/medline SP - 1568 EP - 75 JF - Neurology JO - Neurology VL - 78 IS - 20 N2 - OBJECTIVE: To assess the relationship between Alzheimer disease (AD)-related pathologic changes in frontal cortical brain biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships of AD biomarkers in CSF and cortical biopsy with the final clinical diagnosis of AD. METHODS: In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), Aβ plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF Aβ42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia. RESULTS: The patients with Aβ plaques in the cortical biopsy had lower (p = 0.009) CSF Aβ42 levels than those with no Aβ plaques. The patients with tau in the cortical biopsy had lower (p = 0.014) Aβ42 but higher (p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical biopsy. The patients with amyloid + tau + biopsies had the lowest Aβ42 and highest tau and p-tau 181 levels in CSF. The Aβ42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical Aβ was independently predicted by the APOE ε4 carrier status and age but not by CSF Aβ42 or tau levels. CONCLUSIONS: Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF Aβ42 and high CSF tau and p-tau levels, respectively. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/22517093/CSF_biomarkers_for_Alzheimer_disease_correlate_with_cortical_brain_biopsy_findings_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=22517093 DB - PRIME DP - Unbound Medicine ER -