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

From the Massachusetts Alzheimer Disease Research Center (Drs. Irizarry, Gurol, Raju, Locascio, Tennis, Hyman, Growdon, and Greenberg), Massachusetts General Hospital, Boston, MA; Department of Neurology (Dr. Diaz-Arrastia), University of Texas Southwestern Medical Center, Dallas, TX; Baylor Institute of Metabolic Disease (Dr.Bottiglieri), Dallas, TX.

Address correspondence and reprint requests to Michael C. Irizarry, MD, Alzheimer’s Disease Research Unit, Centers for Aging, Genetics, and Neurodegeneration, Massachusetts General Hospital–East, Building 114, Room 2010, 114 16th Street, Charlestown, MA 02129; e-mail: mirizarry{at}partners.org

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 ß protein (Aß) 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 B₁₂, creatinine, and Aß 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 Aß 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 Aß levels raises the possibility that these circulating factors could interact to affect AD risk and cognition in PD.

Supported by NIH 1T32NS048005-01, AG17861, AG05134 (Massachusetts AD Research Center), AFAR Beeson Award (MCI), and the Lawrence J. and Anne Cable Rubenstein Foundation.

Disclosure: The authors report no conflicts of interest.

Received May 3, 2005. Accepted in final form July 29, 2005.

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