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Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative disease.

Abstract

BACKGROUND

Elevated plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease and is reported to be an independent risk factor for Alzheimer disease (AD) and cognitive decline. tHcy may potentiate neurotoxic and vasculopathic processes, including amyloid beta protein (Abeta) metabolism, implicated in neurodegenerative diseases.

OBJECTIVE

To examine the relationship of plasma total tHcy levels with clinical, demographic, biochemical, and genetic factors in aging, mild cognitive impairment (MCI), AD, cerebral amyloid angiopathy (CAA), and Parkinson disease (PD).

METHODS

Plasma tHcy, folate, vitamin B(12), creatinine, and Abeta levels were assessed in individuals evaluated in the Memory, Stroke, and Movement Disorders Units of Massachusetts General Hospital with diagnoses of AD (n = 145), MCI (n = 47), PD (n = 93), CAA (67), hypertensive intracerebral hemorrhage (hICH) (n = 25), and no dementia (n = 88).

RESULTS

The tHcy levels did not differ across AD, MCI, CAA, hICH, and nondemented control subjects but were increased in the PD group (p < 0.01). The elevated levels within the PD group were due to high tHcy in individuals taking levodopa (p < 0.0001). Increasing tHcy was associated with worse cognition in the PD cases, but not the other diagnostic groups. tHcy levels positively correlated with plasma Abeta levels even after adjustments for age and creatinine (p < 0.0001).

CONCLUSIONS

Mean tHcy levels increased with age but did not discriminate diagnostic groups aside from significant elevation in patients with PD taking levodopa. The positive association between tHcy and plasma Abeta levels raises the possibility that these circulating factors could interact to affect AD risk and cognition in PD.

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  • Authors+Show Affiliations

    ,

    The Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA. mirizarry@partners.org

    , , , , , , , ,

    Source

    Neurology 65:9 2005 Nov 08 pg 1402-8

    MeSH

    Aged
    Aged, 80 and over
    Aging
    Alzheimer Disease
    Amyloid beta-Peptides
    Brain
    Causality
    Cerebral Amyloid Angiopathy
    Cognition Disorders
    Creatinine
    Female
    Folic Acid
    Homocysteine
    Humans
    Levodopa
    Male
    Memory Disorders
    Middle Aged
    Neurodegenerative Diseases
    Parkinson Disease
    Predictive Value of Tests
    Vitamin B 12

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    16275827

    Citation

    Irizarry, M C., et al. "Association of Homocysteine With Plasma Amyloid Beta Protein in Aging and Neurodegenerative Disease." Neurology, vol. 65, no. 9, 2005, pp. 1402-8.
    Irizarry MC, Gurol ME, Raju S, et al. Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative disease. Neurology. 2005;65(9):1402-8.
    Irizarry, M. C., Gurol, M. E., Raju, S., Diaz-Arrastia, R., Locascio, J. J., Tennis, M., ... Bottiglieri, T. (2005). Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative disease. Neurology, 65(9), pp. 1402-8.
    Irizarry MC, et al. Association of Homocysteine With Plasma Amyloid Beta Protein in Aging and Neurodegenerative Disease. Neurology. 2005 Nov 8;65(9):1402-8. PubMed PMID: 16275827.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative disease. AU - Irizarry,M C, AU - Gurol,M E, AU - Raju,S, AU - Diaz-Arrastia,R, AU - Locascio,J J, AU - Tennis,M, AU - Hyman,B T, AU - Growdon,J H, AU - Greenberg,S M, AU - Bottiglieri,T, PY - 2005/11/9/pubmed PY - 2006/4/13/medline PY - 2005/11/9/entrez SP - 1402 EP - 8 JF - Neurology JO - Neurology VL - 65 IS - 9 N2 - BACKGROUND: Elevated plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease and is reported to be an independent risk factor for Alzheimer disease (AD) and cognitive decline. tHcy may potentiate neurotoxic and vasculopathic processes, including amyloid beta protein (Abeta) metabolism, implicated in neurodegenerative diseases. OBJECTIVE: To examine the relationship of plasma total tHcy levels with clinical, demographic, biochemical, and genetic factors in aging, mild cognitive impairment (MCI), AD, cerebral amyloid angiopathy (CAA), and Parkinson disease (PD). METHODS: Plasma tHcy, folate, vitamin B(12), creatinine, and Abeta levels were assessed in individuals evaluated in the Memory, Stroke, and Movement Disorders Units of Massachusetts General Hospital with diagnoses of AD (n = 145), MCI (n = 47), PD (n = 93), CAA (67), hypertensive intracerebral hemorrhage (hICH) (n = 25), and no dementia (n = 88). RESULTS: The tHcy levels did not differ across AD, MCI, CAA, hICH, and nondemented control subjects but were increased in the PD group (p < 0.01). The elevated levels within the PD group were due to high tHcy in individuals taking levodopa (p < 0.0001). Increasing tHcy was associated with worse cognition in the PD cases, but not the other diagnostic groups. tHcy levels positively correlated with plasma Abeta levels even after adjustments for age and creatinine (p < 0.0001). CONCLUSIONS: Mean tHcy levels increased with age but did not discriminate diagnostic groups aside from significant elevation in patients with PD taking levodopa. The positive association between tHcy and plasma Abeta levels raises the possibility that these circulating factors could interact to affect AD risk and cognition in PD. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/16275827/Association_of_homocysteine_with_plasma_amyloid_beta_protein_in_aging_and_neurodegenerative_disease_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&amp;pmid=16275827 DB - PRIME DP - Unbound Medicine ER -