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From Clinical Trials Unit and Memory Disorders Unit (M.E.G., M.C.I., E.E.S., S.R., J.R., J.H.G., S.M.G.), Department of Neurology, Massachusetts General Hospital, Boston; Department of Neurology (R.D.-A.), University of Texas Southwestern Medical Center, Dallas; and Baylor Institute of Metabolic Disease (T.B.), Dallas, TX.
Address correspondence and reprint requests to Dr. Steven M. Greenberg, Wang ACC 836, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114; e-mail: sgreenberg{at}partners.org
Background: Microvascular brain injury, typically measured by extent of white matter hyperintensity (WMH) on MRI, is an important contributor to cognitive impairment in the elderly. Recent studies suggest a role for circulating ß-amyloid peptide in microvascular dysfunction and white matter disease.
Methods: The authors performed a cross-sectional study of clinical, biochemical, and genetic factors associated with WMH in 54 subjects with Alzheimer disease (AD) or mild cognitive impairment (AD/MCI) and an independent group of 42 subjects with cerebral amyloid angiopathy (CAA). Extent of WMH was determined by computer-assisted volumetric measurement normalized to intracranial size (nWMH). Biochemical measurements included plasma concentrations of the 40- and 42-amino acid species of ß-amyloid (Aß40 and Aß42) detected by specific enzyme-linked immunosorbent assays.
Results: Plasma Aß40 concentrations were associated with nWMH in both groups (correlation coefficient = 0.48 in AD/MCI, 0.42 in CAA, p 
0.005). Plasma Aß40 remained independently associated with nWMH after adjustment for potential confounders among age, hypertension, diabetes, homocysteine, creatinine, folate, vitamin B12, and APOE genotype. The presence of lacunar infarctions was also associated with increased Aß40 in both groups. nWMH was greater in CAA (19.8 cm3) than AD (11.1 cm3) or MCI (10.0 cm3; p < 0.05 for both comparisons).
Conclusions: Plasma ß-amyloid 40 concentration is independently associated with extent of white matter hyperintensity in subjects with Alzheimer disease, mild cognitive impairment, or cerebral amyloid angiopathy. If confirmed in longitudinal studies, these data would suggest circulating ß-amyloid peptide as a novel biomarker or risk factor for microvascular damage in these common diseases of the elderly.
Editorial, see page 6
Supported by the NIH (R01 NS04140, T32 NS048005, and P50 AG05134) and the Lawrence J. and Anne Cable Rubenstein Foundation.
Disclosure: The authors report no conflicts of interest.
Received June 20, 2005. Accepted in final form September 19, 2005.
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