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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.
Biol Psychiatry 2004; 56(9):670-6BP

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.

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.govNo 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)

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 -