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Clinical and pathological correlates of apolipoprotein E epsilon 4 in Alzheimer's disease.
Ann Neurol 1996; 39(1):62-70AN

Abstract

Inheritance of the apolipoprotein E (apoE) epsilon 4 allele is associated with a high likelihood of developing Alzheimer's disease (AD). The pathophysiologic basis of this genetic influence is unknown. We reasoned that understanding the influence of apoE epsilon 4 on the clinical course and neuropathological features of AD may provide tests of potential mechanisms. We carried out a prospective longitudinal study to compare the age of onset, duration, and rate of progression of 359 AD patients to apoE genotype. Thirty-one of the individuals who died during the study were available for quantitative neuropathological evaluation. Statistically unbiased stereological counts of neurofibrillary tangles (NFTs) and A beta deposits were assessed in a high-order association cortex, the superior temporal sulcus. Analysis of clinical parameters compared with apoE genotype showed that the epsilon 4 allele is associated with an earlier age of onset but no change in rate of progression of dementia. Quantitative neuropathological assessment revealed that NFTs were strongly associated with clinical measures of dementia duration and severity but not with apoE genotype. A beta deposition, by contrast, was not related to clinical features but was elevated in association with apoE epsilon 4. These results indicate that apoE epsilon 4 is associated with selective clinical and neuropathological features of AD and support hypotheses that focus on an influence of apoE epsilon 4 on amyloid deposition.

Authors+Show Affiliations

Neurology Service, Massachusetts General Hospital, Boston, MA 02114, USA.No 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, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8572669

Citation

Gomez-Isla, T, et al. "Clinical and Pathological Correlates of Apolipoprotein E Epsilon 4 in Alzheimer's Disease." Annals of Neurology, vol. 39, no. 1, 1996, pp. 62-70.
Gomez-Isla T, West HL, Rebeck GW, et al. Clinical and pathological correlates of apolipoprotein E epsilon 4 in Alzheimer's disease. Ann Neurol. 1996;39(1):62-70.
Gomez-Isla, T., West, H. L., Rebeck, G. W., Harr, S. D., Growdon, J. H., Locascio, J. J., ... Hyman, B. T. (1996). Clinical and pathological correlates of apolipoprotein E epsilon 4 in Alzheimer's disease. Annals of Neurology, 39(1), pp. 62-70.
Gomez-Isla T, et al. Clinical and Pathological Correlates of Apolipoprotein E Epsilon 4 in Alzheimer's Disease. Ann Neurol. 1996;39(1):62-70. PubMed PMID: 8572669.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical and pathological correlates of apolipoprotein E epsilon 4 in Alzheimer's disease. AU - Gomez-Isla,T, AU - West,H L, AU - Rebeck,G W, AU - Harr,S D, AU - Growdon,J H, AU - Locascio,J J, AU - Perls,T T, AU - Lipsitz,L A, AU - Hyman,B T, PY - 1996/1/1/pubmed PY - 1996/1/1/medline PY - 1996/1/1/entrez SP - 62 EP - 70 JF - Annals of neurology JO - Ann. Neurol. VL - 39 IS - 1 N2 - Inheritance of the apolipoprotein E (apoE) epsilon 4 allele is associated with a high likelihood of developing Alzheimer's disease (AD). The pathophysiologic basis of this genetic influence is unknown. We reasoned that understanding the influence of apoE epsilon 4 on the clinical course and neuropathological features of AD may provide tests of potential mechanisms. We carried out a prospective longitudinal study to compare the age of onset, duration, and rate of progression of 359 AD patients to apoE genotype. Thirty-one of the individuals who died during the study were available for quantitative neuropathological evaluation. Statistically unbiased stereological counts of neurofibrillary tangles (NFTs) and A beta deposits were assessed in a high-order association cortex, the superior temporal sulcus. Analysis of clinical parameters compared with apoE genotype showed that the epsilon 4 allele is associated with an earlier age of onset but no change in rate of progression of dementia. Quantitative neuropathological assessment revealed that NFTs were strongly associated with clinical measures of dementia duration and severity but not with apoE genotype. A beta deposition, by contrast, was not related to clinical features but was elevated in association with apoE epsilon 4. These results indicate that apoE epsilon 4 is associated with selective clinical and neuropathological features of AD and support hypotheses that focus on an influence of apoE epsilon 4 on amyloid deposition. SN - 0364-5134 UR - https://www.unboundmedicine.com/medline/citation/8572669/Clinical_and_pathological_correlates_of_apolipoprotein_E_epsilon_4_in_Alzheimer's_disease_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0364-5134&date=1996&volume=39&issue=1&spage=62 DB - PRIME DP - Unbound Medicine ER -