Subthreshold amyloid and its biological and clinical meaning: Long way ahead

Gerard N. Bischof*, Heidi I. L. Jacobs

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

32 Citations (Web of Science)

Abstract

The development of in vivo imaging of the pathologic hallmark of Alzheimer disease (AD), beta-amyloid (A beta), altered the framing of its pathophysiology and formulation of inclusion criteria for clinical trials. Recent evidence suggests that in vivo measures of A beta deposition below a threshold indicative of A beta positivity carry critical information on future cognitive decline and accumulation of AD pathology, potentially already at a younger age. Here, we integrate the existing literature on histopathology of A beta and its convergence and divergence with in vivo A beta imaging. The evidence presented amounts to a reconceptualization, in which we advocate for a closer look into A beta accumulation rates in earlier life, the factors that promote accumulation, comparative studies with different markers of A beta, and longitudinal designs to elucidate when AD pathology rises and how it shifts from benign to malignant stages that ultimately define AD. These efforts open a new window of opportunity for disease-modifying interventions.

Original languageEnglish
Pages (from-to)72-79
Number of pages8
JournalNeurology
Volume93
Issue number2
DOIs
Publication statusPublished - 9 Jul 2019

Keywords

  • POSITRON-EMISSION-TOMOGRAPHY
  • PRECLINICAL ALZHEIMER-DISEASE
  • COGNITIVE DECLINE
  • NEUROPATHOLOGIC ASSESSMENT
  • NONDEMENTED INDIVIDUALS
  • BETA
  • DEPOSITION
  • PET
  • PATHOLOGY
  • BURDEN

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