Alzheimer’s Disease Neuroimaging Initiative Grand Opportunity (ADNI Go)

Alzheimer’s Disease Neuroimaging Initiative Grand Opportunity (ADNI Go)

The goal of this project is to determine the relationships among the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of the early (pre-dementia) stages of Alzheimer’s disease (AD). The project builds on the NIA-currently funded AD Neuroimaging Initiative (ADNI1), a collaboration between academia and industry to study biomarkers of AD. This project also serves as a bridge to the renewal of ADNI (termed ADNI2). Herein we continue ADNI themes with new hypotheses informed by our results. Our model posits that AD begins with amyloid β (Aβ) deposition in cortex, which leads to synaptic dysfunction, neurodegeneration, and cognitive/ functional decline. This predicts that the earliest detectable changes (measured in the ADNI-GO projects) are those related to Aβ (Cerebrospinal fluid (CSF) and PET amyloid imaging). Subsequently neurodegeneration is detected by a rise of CSF tau species, synaptic dysfunction by FDG-PET and neuron loss indicated by atrophy most notably in medial temporal lobe (measured with MRI). These changes ultimately lead to memory loss, general cognitive decline and eventually dementia. Expression of each element of AD pathology (e.g. Aβ and tau deposits, atrophy) is influenced by modifying factors including age, APOE genotype, and cerebrovascular disease (white matter lesions detected by FLAIR MRI) and microbleeds (detected by T2* MRI). The results obtained from this grant, together with ADNI1 and ADNI2 will advance understanding of AD pathophysiology, improve diagnostic methods for early detection of AD and improve clinical trial design.

Last Updated: 02-18-2015
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