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

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

Research output: Contribution to journalArticle

115 Citations (Scopus)

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), 18fluorodeoxyglucose (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.

Original languageEnglish (US)
Pages (from-to)472-480
Number of pages9
JournalAnnals of Neurology
Volume73
Issue number4
DOIs
StatePublished - Apr 2013

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Amyloid
Brain Injuries
Biomarkers
Positron-Emission Tomography
Alzheimer Disease
Magnetic Resonance Spectroscopy
Brain
Apolipoprotein E4
Parkinsonian Disorders
Amyloidosis
Genotype
Alzheimer disease, familial, type 3

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Brain injury biomarkers are not dependent on β-amyloid in normal elderly. / Knopman, David S; Jack, Clifford R Jr.; Wiste, Heather J.; Weigand, Stephen D.; Vemuri, Prashanthi D; Lowe, Val; Kantarci, Kejal M; Gunter, Jeffrey L.; Senjem, Matthew L.; Mielke, Michelle M; Roberts, Rosebud O; Boeve, Bradley F; Petersen, Ronald Carl.

In: Annals of Neurology, Vol. 73, No. 4, 04.2013, p. 472-480.

Research output: Contribution to journalArticle

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AU - Vemuri, Prashanthi D

AU - Lowe, Val

AU - Kantarci, Kejal M

AU - Gunter, Jeffrey L.

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AU - Roberts, Rosebud O

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AU - Petersen, Ronald Carl

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