Stable Size Distribution of Amyloid Plaques Over the Course of Alzheimer Disease (original) (raw)

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MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital,

Massachusetts Alzheimer Disease Research Center

, and Harvard Medical School, Charlestown

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MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital,

Massachusetts Alzheimer Disease Research Center

, and Harvard Medical School, Charlestown

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Massachusetts General Hospital Biostatistics Center

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Teresa Gómez-Isla, MD, PhD

MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital,

Massachusetts Alzheimer Disease Research Center

, and Harvard Medical School, Charlestown

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MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital,

Massachusetts Alzheimer Disease Research Center

, and Harvard Medical School, Charlestown

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MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital,

Massachusetts Alzheimer Disease Research Center

, and Harvard Medical School, Charlestown

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Rebecca A. Betensky, PhD, MPH

MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital,

Massachusetts Alzheimer Disease Research Center

, and Harvard Medical School, Charlestown

Department of Biostatistics, Harvard School of Public Health

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Matthew P. Frosch, MD, PhD

MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital,

Massachusetts Alzheimer Disease Research Center

, and Harvard Medical School, Charlestown

C. S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Boston, Massachusetts

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Bradley T. Hyman, MD, PhD

MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital,

Massachusetts Alzheimer Disease Research Center

, and Harvard Medical School, Charlestown

Send correspondence and reprint requests to: Bradley T. Hyman, MD, PhD, Bldg 114, 16th St 2009, Charlestown, MA 02129-4404; E-mail: bhyman@partners.org

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Published:

01 August 2012

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Alberto Serrano-Pozo, Matthew L. Mielke, Alona Muzitansky, Teresa Gómez-Isla, John H. Growdon, Brian J. Bacskai, Rebecca A. Betensky, Matthew P. Frosch, Bradley T. Hyman, Stable Size Distribution of Amyloid Plaques Over the Course of Alzheimer Disease, Journal of Neuropathology & Experimental Neurology, Volume 71, Issue 8, August 2012, Pages 694–701, https://doi.org/10.1097/NEN.0b013e31825e77de
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Abstract

Amyloid β plaques are a key pathologic feature of Alzheimer disease (AD), but whether plaque sizes increase or stabilize over the course of AD is unknown. We measured the size distribution of total immunoreactive (10D5-positive) and dense-core (Thioflavin S-positive) plaques in the temporal neocortex of a large group of subjects with AD and age-matched plaque-bearing subjects without dementia to test the hypothesis that Amyloid plaques continue to grow along with the progression of the disease. The size of Amyloid β (10D5)-positive plaques did not differ between groups, whereas dense-core plaques from the group with AD were slightly larger than those from the group without dementia (∼25%-30%, p = 0.01). Within the group with AD, dense-core plaque size did not independently correlate with duration of clinical disease (from 4 to 21 years, p = 0.68), whereas 10D5-positive plaque size correlated negatively with disease duration (p = 0.01). By contrast, an earlier age of symptom onset strongly predicted a larger postmortem plaque size; this effect was independent of disease duration and the presence of the APOEε4 allele (p = 0.0001). We conclude that plaques vary in size among patients, with larger size distributions correlating with an earlier age of onset, but plaques do not substantially increase in size over the clinical course of the disease.

© 2012, by the American Association of Neuropathologists, Inc.

Topic:

• alleles
• amyloid
• alzheimer's disease
• dementia
• age of onset
• autopsy
• neocortex
• senile plaques
• illness length
• symptom onset

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