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Cerebrospinal fluid beta-amyloid1-42 and tau in control subjects at risk for Alzheimer's disease: the effect of APOE epsilon4 allele.

Abstract

BACKGROUND

Cerebrospinal fluid (CSF) measures of beta-amyloid(1-42) and tau are linked with the known neuropathology of Alzheimer's disease (AD). Numerous lines of evidence have also suggested that individuals with at least one APOE epsilon4 allele on chromosome 19 are at increased risk of developing AD. We tested these CSF markers in groups of subjects with AD and healthy older control subjects, using the absence or presence of the APOE epsilon4 allele as a predictive variable in the search for possible prognostic biomarkers of AD.

METHODS

We assessed the levels of beta-amyloid(1-42) and total tau in the CSF of 292 subjects (142 control subjects and 150 subjects with mild-to-moderate AD), who were research participants at the National Institute of Mental Health. The group of control subjects was enriched with a high percentage of subjects with a positive family history of AD. All subjects underwent extensive global cognitive testing.

RESULTS

When divided according to the absence or presence of the APOE epsilon4 allele, the control subjects with at least one epsilon4 allele had significantly lower CSF beta-amyloid(1-42) but not tau levels than control subjects without an APOE epsilon4 allele (p < .01). As expected, the AD patients had lower levels of CSF beta-amyloid(1-42) and higher CSF tau levels than the normal control group (p < .01).

CONCLUSIONS

The association of APOE epsilon4 allele and lower, more AD-like levels of CSF beta-amyloid(1-42) in older control subjects is consistent with previous studies showing possible neuroimaging and cognitive abnormalities with epsilon4 carriers and suggests that CSF beta-amyloid(1-42) decreases might represent an early biomarker of AD. Longitudinal follow-up is of course required to verify whether this biomarker is indeed predictive of clinical conversion to AD.

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  • Authors+Show Affiliations

    ,

    National Institute of Mental Health, Geriatric Psychiatry Branch, Building 10, Room 3N228, 9000 Rockville Pike, Bethesda, MD 20892, USA. trey@mail.nih.gov

    , , , , , , , , , , , ,

    Source

    Biological psychiatry 56:9 2004 Nov 01 pg 670-6

    MeSH

    Age Factors
    Aged
    Alleles
    Alzheimer Disease
    Amyloid beta-Peptides
    Apolipoprotein E4
    Apolipoproteins E
    Chi-Square Distribution
    Demography
    Enzyme-Linked Immunosorbent Assay
    Female
    Genotype
    Humans
    Male
    Middle Aged
    Neuropsychological Tests
    Peptide Fragments
    Risk
    Spinal Puncture
    tau Proteins

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    15522251

    Citation

    Sunderland, Trey, et al. "Cerebrospinal Fluid Beta-amyloid1-42 and Tau in Control Subjects at Risk for Alzheimer's Disease: the Effect of APOE Epsilon4 Allele." Biological Psychiatry, vol. 56, no. 9, 2004, pp. 670-6.
    Sunderland T, Mirza N, Putnam KT, et al. Cerebrospinal fluid beta-amyloid1-42 and tau in control subjects at risk for Alzheimer's disease: the effect of APOE epsilon4 allele. Biol Psychiatry. 2004;56(9):670-6.
    Sunderland, T., Mirza, N., Putnam, K. T., Linker, G., Bhupali, D., Durham, R., ... Cohen, R. M. (2004). Cerebrospinal fluid beta-amyloid1-42 and tau in control subjects at risk for Alzheimer's disease: the effect of APOE epsilon4 allele. Biological Psychiatry, 56(9), pp. 670-6.
    Sunderland T, et al. Cerebrospinal Fluid Beta-amyloid1-42 and Tau in Control Subjects at Risk for Alzheimer's Disease: the Effect of APOE Epsilon4 Allele. Biol Psychiatry. 2004 Nov 1;56(9):670-6. PubMed PMID: 15522251.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cerebrospinal fluid beta-amyloid1-42 and tau in control subjects at risk for Alzheimer's disease: the effect of APOE epsilon4 allele. AU - Sunderland,Trey, AU - Mirza,Nadeem, AU - Putnam,Karen T, AU - Linker,Gary, AU - Bhupali,Deepa, AU - Durham,Rob, AU - Soares,Holly, AU - Kimmel,Lida, AU - Friedman,David, AU - Bergeson,Judy, AU - Csako,Gyorgy, AU - Levy,James A, AU - Bartko,John J, AU - Cohen,Robert M, PY - 2004/06/01/received PY - 2004/07/30/revised PY - 2004/07/31/accepted PY - 2004/11/4/pubmed PY - 2005/2/3/medline PY - 2004/11/4/entrez SP - 670 EP - 6 JF - Biological psychiatry JO - Biol. Psychiatry VL - 56 IS - 9 N2 - BACKGROUND: Cerebrospinal fluid (CSF) measures of beta-amyloid(1-42) and tau are linked with the known neuropathology of Alzheimer's disease (AD). Numerous lines of evidence have also suggested that individuals with at least one APOE epsilon4 allele on chromosome 19 are at increased risk of developing AD. We tested these CSF markers in groups of subjects with AD and healthy older control subjects, using the absence or presence of the APOE epsilon4 allele as a predictive variable in the search for possible prognostic biomarkers of AD. METHODS: We assessed the levels of beta-amyloid(1-42) and total tau in the CSF of 292 subjects (142 control subjects and 150 subjects with mild-to-moderate AD), who were research participants at the National Institute of Mental Health. The group of control subjects was enriched with a high percentage of subjects with a positive family history of AD. All subjects underwent extensive global cognitive testing. RESULTS: When divided according to the absence or presence of the APOE epsilon4 allele, the control subjects with at least one epsilon4 allele had significantly lower CSF beta-amyloid(1-42) but not tau levels than control subjects without an APOE epsilon4 allele (p < .01). As expected, the AD patients had lower levels of CSF beta-amyloid(1-42) and higher CSF tau levels than the normal control group (p < .01). CONCLUSIONS: The association of APOE epsilon4 allele and lower, more AD-like levels of CSF beta-amyloid(1-42) in older control subjects is consistent with previous studies showing possible neuroimaging and cognitive abnormalities with epsilon4 carriers and suggests that CSF beta-amyloid(1-42) decreases might represent an early biomarker of AD. Longitudinal follow-up is of course required to verify whether this biomarker is indeed predictive of clinical conversion to AD. SN - 0006-3223 UR - https://www.unboundmedicine.com/medline/citation/15522251/Cerebrospinal_fluid_beta_amyloid1_42_and_tau_in_control_subjects_at_risk_for_Alzheimer's_disease:_the_effect_of_APOE_epsilon4_allele_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-3223(04)00855-8 DB - PRIME DP - Unbound Medicine ER -