. Emerging β-amyloid pathology and accelerated cortical atrophy. JAMA Neurol. 2014 Jun;71(6):725-34. PubMed.


Please login to recommend the paper.


  1. This study is an excellent example of the importance of longitudinal biomarker studies in different stages of AD, from the preclinical to the dementia stage.

    Just as the map of the world was redrawn after the introduction of modern technology, knowledge about the evolution of AD pathology likely will have to be reconsidered based on this type of study. The basis for this knowledge will expand from end-stage neuropathology in cross-sectional clinical studies to longitudinal biomarker studies, including those in the preclinical stage of the disease. Indeed, the authors conclude that the results from this study will modify previous models of the relationship between Aβ and regional atrophy during the development of AD.

  2. In this article, Mattson et al. examine gray-matter atrophy in clinically normal (CN) participants with 1) high and stable levels of CSF Aβ (s-Aβneg), 2) high and declining levels of CSF Aβ, and 3) low levels of CSF Aβ (ABpos). Although gray-matter differences between groups were not observed at baseline, d-Aβneg CNs showed greater frontoparietal atrophy over time, whereas a more diffuse pattern of atrophy was observed in Aβpos normal controls. Interestingly, these gray-matter changes were not accompanied by changes in CSF tau measures, suggesting this pattern of atrophy may occur independently of tangle formation during the early stages of Aβ accumulation.

    Although limited by a small sample size, these results suggest that initial changes in the trajectory towards Alzheimer’s disease may occur in neocortical areas known to show early Aβ deposition.  The spatial pattern of Aβ deposition during the earliest stages of accumulation within CNs remains unknown, and it would be interesting to use amyloid imaging to examine whether frontoparietal regions are among the first regions to show it.  A major remaining question is why does frontoparietal atrophy slow down over time?  It is possible that this early effect in frontoparietal regions is purely related to Aβ, given that these regions typically do not show tangle pathology until late in the disease.  Thus, more drastic effects may eventually occur in regions displaying con-current amyloid and tangle pathologies, such as in temporal cortex. To understand these distinct patterns of regional vulnerabilities, it will be critical to investigate longer follow ups of CNs undergoing the earliest signs of Aβ accumulation. 

Make a Comment

To make a comment you must login or register.

This paper appears in the following:


  1. Do Frontoparietal Regions Shrink First in Preclinical Alzheimer’s?