%0 Journal Article %J J Alzheimers Dis %D 2016 %T Application of the IWG-2 Diagnostic Criteria for Alzheimer's Disease to the ADNI. %A Wang, Hui-Fu %A Tan, Lan %A Cao, Lei %A Zhu, Xi-Chen %A Jiang, Teng %A Tan, Meng-Shan %A Liu, Ying %A Wang, Chong %A Tsai, Richard M %A Jia, Jian-Ping %A Yu, Jin-Tai %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Amyloid Precursor Protein Secretases %K Aspartic Acid Endopeptidases %K Cognitive Dysfunction %K Databases, Factual %K Disease Progression %K Female %K Humans %K Longitudinal Studies %K Male %K Multicenter Studies as Topic %K Neuroimaging %K Psychiatric Status Rating Scales %K tau Proteins %X

BACKGROUND: The International Working Group (IWG) recently proposed the revised diagnostic criteria for Alzheimer's disease (AD) to define and refine several types of AD, and to reclassify AD-related biomarkers into diagnostic and progression markers, but its performance is not known.

OBJECTIVE: This study was designed to describe the application of the revised IWG criteria in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and to ascertain whether diagnostic and progression markers show significant differences in their relationships to AD severity and progression.

METHODS: Based on the requirements of the refined criteria, 857 ADNI subjects with memory evaluation and at least one pathophysiological marker (CSF or amyloid imaging biomarkers) were eligible and reclassified in this study, and we calculated the associations of diagnostic (CSF and amyloid PET) and progression markers (MRI and fluorodeoxyglucose-PET) with AD severity and progression respectively.

RESULTS: The majority (84.2% ) of ADNI AD group (n = 117) and 173 MCI (37.4% ) subjects in ADNI met the definition of typical AD; and 105 cognitively normal (41.0% ) individuals were diagnosed as asymptomatic AD. Furthermore, diagnostic and progression markers showed significant differences when correlated to AD severity and progression.

CONCLUSION: A large proportion of AD dementia subjects were categorized as typical AD, and the revised criteria could identify typical AD from MCI status as well as asymptomatic AD at the asymptomatic stage. Moreover, the significant differences between diagnostic and progression markers further supported the new biomarkers categorization in the refined criteria.

%B J Alzheimers Dis %V 51 %P 227-36 %8 2016 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/26836176?dopt=Abstract %R 10.3233/JAD-150824 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Bridging Integrator 1 (BIN1) Genotypes Mediate Alzheimer's Disease Risk by Altering Neuronal Degeneration. %A Wang, Hui-Fu %A Wan, Yu %A Hao, Xiao-Ke %A Cao, Lei %A Zhu, Xi-Chen %A Jiang, Teng %A Tan, Meng-Shan %A Tan, Lin %A Zhang, Dao-Qiang %A Tan, Lan %A Yu, Jin-Tai %K Adaptor Proteins, Signal Transducing %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Amyloid beta-Peptides %K Biomarkers %K Brain %K Databases, Factual %K European Continental Ancestry Group %K Female %K Follow-Up Studies %K Genetic Predisposition to Disease %K Glucose %K Humans %K Longitudinal Studies %K Magnetic Resonance Imaging %K Male %K Middle Aged %K Nerve Degeneration %K Nuclear Proteins %K Polymorphism, Single Nucleotide %K Positron-Emission Tomography %K Risk %K tau Proteins %K Tumor Suppressor Proteins %X

BACKGROUND: Bridging integrator 1 (BIN1) has been identified as one of the most associated loci for Alzheimer's disease (AD), and recently was reported to modulate tau pathology to mediate AD in vitro. However, the effects of BIN1 on the AD related biomarkers in AD continuum were not specifically assessed.

OBJECTIVE: We explored the effects of BIN1 loci on AD specific biomarkers (CSF proteins, brain structures, glucose and amyloid-β (Aβ) metabolisms) to investigate the role BIN1 in AD pathogenesis.

METHODS: We calculated the associations of BIN1 loci with these markers at baseline and follow-up in multiple linear models in 812 ADNI subjects.

RESULTS: BIN1 loci were significantly associated with the levels of T-tau (rs744373: pc = 0.047, rs13031703: pc = 0.042) and P-tau (rs744373: pc = 0.044, rs13031703: pc = 0.019), but not with Aβ in CSF test. BIN1 genotypes were strongly related to atrophy of hippocampus (rs7561528: pc = 0.011), CA1 (rs1469980: pc = 0.029) and parahippocampus (rs72838284, pc = 0.017) on MRI, and to glucose metabolism on FDG-PET, but not to Aβ deposition on AV45-PET imaging. Furthermore, haplotype and subgroup analysis confirmed these significant findings. In addition, the loci associated with these markers were also identified to influence the risk for AD in the meta-analysis of 74 046 European individuals.

CONCLUSION: This study supported that BIN1 contributes to the risk of AD by altering neural degeneration (abnormal tau, brain atrophy and glucose metabolism) but not Aβ pathology.

%B J Alzheimers Dis %V 52 %P 179-90 %8 2016 03 15 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/27003210?dopt=Abstract %R 10.3233/JAD-150972