With regards to our article “Apolipoprotein E (ApoE) ε4 Does Not Modulate Amyloid-β–Associated Neurodegeneration in Preclinical Alzheimer Disease,” we researched this topic because there is a need to better elucidate the pathobiologic changes underlying the earliest stage of Alzheimer disease (AD). Specifically, we wanted to better understand how ApoE ε4, tau, and amyloid together modulate the earliest neurodegenerative process in cognitively normal older adults. Clinically, our findings suggest the need for examining entities besides amyloid, such as ApoE and tau, when designing anti-amyloid therapeutic trials. Our findings also support the hypothesis that the Alzheimer disease process may involve an amyloid-dependent and an amyloid-independent stage. However, it is still not known whether there exist tau-dependent and tau-independent stages of the disease process, and current work from our laboratory is investigating this issue. That is, there is a need to further understand whether additional entities besides tau modulate β-associated neurodegeneration in preclinical and very mildly symptomatic AD. Taken together, these findings

illustrate that the Alzheimer neurodegenerative process starts very early and is extremely complex, involving interactions between numerous genetic and cellular factors. Only by better understanding this complexity, can we identify meaningful therapeutic targets that will prevent this disease.

Our other manuscript, "Temporoparietal MR Imaging Measures of Atrophy in Subjects with Mild Cognitive Impairment That Predict Subsequent Diagnosis of Alzheimer Disease," was one of the first papers to evaluate the use of semi-automated/automated MRI-based morphometric tools for predicting time to progression from mild cognitive impairment to AD. Specifically, our work demonstrated that semi-automated/automated measures of regional neocortical volumes can predict which individuals with cognitive impairment would progress to AD. Our findings suggest the importance and feasibility of using structural MRI-based tools in the clinical evaluation of memory impairment. Current work from our laboratory has been expanding upon this work to demonstrate that MRI-based measures can be combined with cellular and genetic measures to identify presymptomatic and very mildly symptomatic older individuals at increased risk for AD.

 

Read these articles at AJNR.org . . .

Apolipoprotein E ε4 Does Not Modulate Amyloid-β–Associated Neurodegeneration in Preclinical Alzheimer Disease

Temporoparietal MR Imaging Measures of Atrophy in Subjects with Mild Cognitive Impairment That Predict Subsequent Diagnosis of Alzheimer Disease