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March 2013

Apolipoprotein E, Neurodegeneration, and Alzheimer Disease

Author Affiliations

Author Affiliations: Helen Wills Neuroscience Institute and School of Public Health, University of California, Berkeley.

JAMA Neurol. 2013;70(3):299-300. doi:10.1001/jamaneurol.2013.726

Because of a widespread belief that effective therapies for Alzheimer disease (AD) will require intervention prior to the onset of dementia, intense effort has been devoted to identifying asymptomatic individuals who are likely to develop the disease. Major strategies include biomarker measurement to detect subtle signs of AD in asymptomatic individuals and investigation of people with genetic mutations or polymorphisms indicative of high risk. The biomarkers of greatest interest have been separated into 2 categories, one of which is the measurement of the AD hallmark protein β-amyloid (Aβ), apparent as reduced concentration in cerebrospinal fluid or increased retention of positron emission tomography (PET) tracers that bind to fibrillar Aβ. The second category includes biomarkers that are presumptive measures of neurodegeneration, such as atrophy of the hippocampus and cerebral glucose hypometabolism in the temporoparietal cortex. Genetic and biomarker approaches may be combined, as in the Dominantly Inherited Alzheimer Network, a study of people with mendelian mutations that cause AD. In the Dominantly Inherited Alzheimer Network study, evidence of brain Aβ deposition, glucose hypometabolism, and hippocampal atrophy were seen in asymptomatic mutation carriers 10 to 15 years prior to the expected age at disease onset.1 Charting the temporal course of these biomarker changes provides a basis for defining at-risk populations for treatment selection and informs us about basic mechanisms of disease.

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