. Neural hyperactivation in carriers of the Alzheimer's risk variant on the clusterin gene. Eur Neuropsychopharmacol. 2011 Dec;21(12):880-4. PubMed.

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  1. The three studies all contribute to the field of early diagnosis of Alzheimer's disease by investigating how genetic susceptibility genes (in this case, CLU) affect neuronal activation (Erk et al. and Lancaster et al.) and white matter integrity (Braskie et al.). As new treatments for the disease are underway, early identification of individuals at risk of developing Alzheimer's disease is becoming increasingly critical. Thus, the development of neurogenetic markers of AD-related pathology is important for early intervention and prevention of the disease.

    I found the paper by Erk et al. especially interesting, as they are using a novel approach to identify alterations in brain function by analyzing task data (episodic retrieval) using a functional connectivity approach. The results from both fMRI studies (Erk et al. and Lancaster et al.) are in accordance and converge well with previous findings (including the ones from our lab) demonstrating functional alterations in a specific subset of brain regions, including hippocampus, posteromedial cortex, and prefrontal cortex, in cognitively healthy individuals with high risk of developing AD. Interestingly, as the study by Braskie et al. demonstrated, the same areas where we see functional changes are also affected by early pathological changes, i.e., decreased white matter integrity. Recently, our lab and other groups have shown that the same network of regions demonstrates increased amyloid deposition in cognitively normal individuals, suggesting that functional and pathological brain changes may begin far in advance of symptomatic AD.

    I believe that the development of new techniques, especially in neuroimaging, has advanced our detection capabilities and current understanding of Alzheimer’s disease. As more groups are conducting multimodal imaging studies to look at several sensitive markers at the same time, we have started to develop and optimize cognitive, imaging, and genetic biomarkers to track progression through the early changes in the trajectory of AD, even before any clinical signs.

    In order for us to fully appreciate these findings (Erk et al. and Lancaster et al.) I believe there is a need for longitudinal follow-up of these individuals. To confirm if the pattern that is observed in the "high-risk" group really is a marker of early AD, it would be informative to know how many people convert to AD in the future. A faster approach would be to conduct similar studies but include people with mild cognitive impairment (MCI) and AD to investigate if the pattern observed in the high-risk group resembles the pattern in AD and MCI patients.

    View all comments by Patrizia Vannini

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  1. Neuroimaging Offers a CLU to AD Risk Factor’s Functional Effects