Characterize the Role of Shroom-3 in Alzheimer's Disease

Objectives of the proposed research: Alzheimer's disease (AD), the most common type of dementia, is a neurodegenerative disease that generally affects people greater than 45 years old. AD patients show a persistent cognitive decline that leads to total disability at the end stage. Tau protein is one of major proteins linked to AD progression; it accumulates in neurons and forms paired helical filaments. As a result, Tau protein loses its capability to bind with microtubules and leading to neurodegeneration. We have performed Cdc37 chaperone based mass spectrometry to identify novel proteins linked to AD. We found Shroom-3 interaction with Cdc37 completely abolished in AD brain tissues compared to normal human brain tissues. These data provide strong evidence for potential role of Shroom-3 in AD. Currently, there is no genomic data available on Shroom-3 in AD cases. Hence, with this data access we aimed to perform genomic analysis for Shroom-3 and identify any potential mutations (SNPs) in Shroom-3 in AD. After analyzing Shroom-3, we will look at Cdc37 chaperones and other related proteins to fully characterize Shroom-3 and associated proteins.

Study design: As a pilot study, we will aim for sample size n=100. Depending on available data and information for analysis, we will group samples as follows: male & female, different ethnicity, and age groups. Depending on data analysis results sample size will be adjusted to higher numbers after completion of pilot study with n=100. We will use bioinformatic software to compare gene sequences from AD patients with normal healthy individual (wild-type gene sequences) to identify any potential mutations/ Single nucleotide polymorphisms (SNPS). Based on results, we will plan cellular and animal model studies for further characterization.

Analysis plan, including the phenotypic characteristics that will be evaluated in association with genetic variants: We will carefully look at AD and normal aligned sequences for any changes in a particular nucleotide or set of nucleotides to identify mutations/SNPs in different groups (gender, ethnicity, & age).

Alzheimer's disease (AD), the most common type of dementia, is a neurodegenerative disease that generally affects people greater than 45 years old. AD patients show a persistent cognitive decline that leads to total disability at the end stage. Tau protein is one of major proteins linked to AD progression; it accumulates in neurons and forms paired helical filaments. As a result, Tau protein loses its capability to bind with microtubules and leading to neurodegeneration. We have performed Cdc37 chaperone based mass spectrometry to identify novel proteins linked to AD. We found Shroom-3 interaction with Cdc37 completely abolished in AD brain tissues compared to normal human brain tissues. These data provide strong evidence for potential role of Shroom-3 in AD. Currently, there is no genomic data available on Shroom-3 in AD cases. Hence, with this data access we aimed to perform genomic analysis for Shroom-3 and identify any potential mutations (SNPs) in Shroom-3 in AD. We will also look at Cdc37 chaperones and related proteins to fully characterize Shroom-3 and associated proteins.