PET Amyloid and Tau Status Are Differently Affected by Patient Features

J Alzheimers Dis. 2020;78(3):1129-1136. doi: 10.3233/JAD-200124.

Abstract

Background: Amyloid-β (Aβ) plaques and tau neurofibrillary tangles are two neuropathological hallmarks of Alzheimer's disease (AD), which both can be visualized in vivo using PET radiotracers, opening new opportunities to study disease mechanisms.

Objective: Our study investigated 11 non-PET factors in 5 categories (including demographic, clinical, genetic, MRI, and cerebrospinal fluid (CSF) features) possibly affecting PET amyloid and tau status to explore the relationships between amyloid and tau pathology, and whether these features had a different association with amyloid and tau status.

Methods: We included 372 nondemented elderly from the Alzheimer's Disease Neuroimaging Initiative cohort. All underwent PET amyloid and tau analysis simultaneously, and were grouped into amyloid/tau quadrants based on previously established abnormality cut points. We examined the associations of above selected features with PET amyloid and tau status using a multivariable logistic regression model, then explored whether there was an obvious correlation between the significant features and PET amyloid or tau levels.

Results: Our results demonstrated that PET amyloid and tau status were differently affected by patient features, and CSF biomarker features provided most significant values associating PET findings. CSF Aβ42/40 was the most important factor affecting amyloid PET status, and negatively correlated with amyloid PET levels. CSF pTau could significantly influence both amyloid and tau PET status. Besides CSF pTau and Aβ42, APOEɛ4 allele status and Mini-Mental State Examination scores also could influence tau PET status, and significantly correlated with tau PET levels.

Conclusion: Our results support that tau pathology possibly affected by Aβ-independent factors, implicating the importance of tau pathology in AD pathogenesis.

Keywords: APOE; Alzheimer’s disease; Mini-Mental State Examination; PET; amyloid-β; biomarker; cerebrospinal fluid; tau.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds
  • Apolipoprotein E4 / genetics
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Carbolines
  • Case-Control Studies
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / diagnostic imaging*
  • Contrast Media
  • Ethylene Glycols
  • Female
  • Hippocampus / diagnostic imaging
  • Hippocampus / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mental Status and Dementia Tests
  • Middle Aged
  • Organ Size
  • Peptide Fragments / cerebrospinal fluid
  • Positron-Emission Tomography
  • tau Proteins / cerebrospinal fluid
  • tau Proteins / metabolism*

Substances

  • Amyloid beta-Peptides
  • Aniline Compounds
  • Apolipoprotein E4
  • Carbolines
  • Contrast Media
  • Ethylene Glycols
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • tau Proteins
  • florbetapir
  • 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

Grants and funding