Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Apr;73(4):472-80.
doi: 10.1002/ana.23816. Epub 2013 Feb 19.

Brain injury biomarkers are not dependent on β-amyloid in normal elderly

David S Knopman  1 , Clifford R Jack Jr, Heather J Wiste, Stephen D Weigand, Prashanthi Vemuri, Val J Lowe, Kejal Kantarci, Jeffrey L Gunter, Matthew L Senjem, Michelle M Mielke, Rosebud O Roberts, Bradley F Boeve, Ronald C Petersen
Affiliations

Brain injury biomarkers are not dependent on β-amyloid in normal elderly

David S Knopman et al. Ann Neurol. 2013 Apr.

Abstract

Objective: The new criteria for preclinical Alzheimer disease (AD) proposed 3 stages: abnormal levels of β-amyloid (stage 1), stage 1 plus evidence of brain injury (stage 2), and stage 2 plus subtle cognitive changes (stage 3). However, a large group of subjects with normal β-amyloid biomarkers have evidence of brain injury; we labeled them as the "suspected non-Alzheimer pathophysiology" (sNAP) group. The characteristics of the sNAP group are poorly understood.

Methods: Using the preclinical AD classification, 430 cognitively normal subjects from the Mayo Clinic Study of Aging who underwent brain magnetic resonance (MR), (18)fluorodeoxyglucose (FDG), and Pittsburgh compound B positron emission tomography (PET) were evaluated for FDG PET regional volumetrics, MR regional brain volumetrics, white matter hyperintensity volume, and number of infarcts. We examined cross-sectional associations across AD preclinical stages, those with all biomarkers normal, and the sNAP group.

Results: The sNAP group had a lower proportion (14%) with apolipoprotein E ε4 genotype than the preclinical AD stages 2 + 3. The sNAP group did not show any group differences compared to stages 2 + 3 of the preclinical AD group on measures of FDG PET regional hypometabolism, MR regional brain volume loss, cerebrovascular imaging lesions, vascular risk factors, imaging changes associated with α-synucleinopathy, or physical findings of parkinsonism.

Interpretation: Cognitively normal persons with brain injury biomarker abnormalities, with or without abnormal levels of β-amyloid, were indistinguishable on a variety of imaging markers, clinical features, and risk factors. The initial appearance of brain injury biomarkers that occurs in cognitively normal persons with preclinical AD may not depend on β-amyloidosis.

PubMed Disclaimer

References

    1. Sperling RA, Aisen P, Beckett L, et al. Towards defining the preclinical stage of Alzheimer’s Disease: Recommendations from the National Institute on Aging and the Alzheimer’s Association Workgroup. Alzheimer’s & Dementia: Journal of the Alzheimer’s Association. 2011;7:280–92. - PMC - PubMed
    1. Jack CRJ, Knopman DS, Weigand SD, et al. An operational approach to National Institute on Aging-Alzheimer’s Association criteria for preclinical Alzheimer disease. Ann Neurol. 2012;71:765–75. - PMC - PubMed
    1. Knopman DS, Jack CRJ, Wiste HJ, et al. Short-term Clinical Outcomes for Stages of NIA-AA Preclinical Alzheimer Disease. Neurology. 2012;78:1576–82. - PMC - PubMed
    1. Roberts RO, Geda YE, Knopman D, et al. The Mayo Clinic Study of Aging: Design and Sampling, Participation, Baseline Measures and Sample Characteristics. Neuroepidemiology. 2008;30:58–69. - PMC - PubMed
    1. Petersen RC, Roberts RO, Knopman DS, et al. Prevalence of mild cognitive impairment is higher in men than in women. The Mayo Clinic Study of Aging Neurology. 2010;75:889–897. - PMC - PubMed

Publication types

LinkOut - more resources