Odor identification score as an alternative method for early identification of amyloidogenesis in Alzheimer's disease.

A simple screening test to identify the early stages of Alzheimer's disease (AD) is urgently needed. We investigated whether odor identification impairment can be used to differentiate between stages of the A/T/N classification (amyloid,  tau, neurodegeneration) in individuals with amnestic mild cognitive impairment or AD and in healthy controls. We collected data from 132 Japanese participants visiting the Toranomon Hospital dementia outpatient clinic. The odor identification scores correlated significantly with major neuropsychological scores, regardless of apolipoprotein E4 status, and with effective cerebrospinal fluid (CSF) biomarkers [amyloid ß 42 (Aß42) and the Aß42/40 and phosphorylated Tau (p-Tau)/Aß42 ratios] but not with ineffective biomarkers [Aß40 and the p-Tau/total Tau ratio]. A weak positive correlation was observed between the corrected odor identification score (adjusted for age, sex, ApoE4 and MMSE), CSF Aß42, and the Aß42/40 ratio. The odor identification score demonstrated excellent discriminative power for the amyloidogenesis stage , according to the A/T/N classification, but was unsuitable for differentiating between the p-Tau accumulation and the neurodegeneration stages. After twelve odor species were analyzed, a version of the score comprising only four odors-India ink, wood, curry, and sweaty socks-proved highly effective in identifying AD amyloidogenesis, showing promise for the screening of preclinical AD.

Extracellular vesicle proteome unveils cathepsin B connection to Alzheimer's disease pathogenesis.

Extracellular vesicles (EVs) are membrane vesicles that are released extracellularly and considered to be implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease. Here, CSF EVs of 16 ATN-classified cases were subjected to quantitative proteome analysis. In these CSF EVs, levels of 11 proteins were significantly altered during the ATN stage transitions (P < 0.05 and fold-change > 2.0). These proteins were thought to be associated with Alzheimer's disease pathogenesis and represent candidate biomarkers for pathogenic stage classification. Enzyme-linked immunosorbent assay analysis of CSF and plasma EVs revealed altered levels of cathepsin B (CatB) during the ATN transition (seven ATN groups in validation set, n = 136). The CSF and plasma EV CatB levels showed a negative correlation with CSF amyloid-ß42 concentrations. This proteomic landscape of CSF EVs in ATN classifications can depict the molecular framework of Alzheimer's disease progression, and CatB may be considered a promising candidate biomarker and therapeutic target in Alzheimer's disease amyloid pathology.

A Validity and Reliability Study of the Japanese Version of the Geriatric Depression Scale 15 (GDS-15-J).

OBJECTIVE: The 15-item Geriatric Depression Scale (GDS-15) is one of the most widely used screening instruments for depression among the elderly. The aim of this study was to examine the validity and reliability of the Japanese version of the GDS-15 (GDS-15-J) in comparison with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for depression. METHODS: The study participants were 128 elderly outpatients (age range, 55 to 92 years) categorized into two groups (76 non-depressive patients, 52 depressive patients) based on the DSM-IV-TR criteria for depression. RESULTS: Logistic regression analysis showed that regardless of age and sex, the GDS-15-J score could be used to screen patients for depression (p < .001). The validity of the GDS-15-J for depression assessed against DSM-IV-TR criteria was excellent based on receiver operating characteristic analysis (optimal cutoff point: 6/7; sensitivity: .98; specificity: .86). The recommended optimal cutoff score when screening for depression is 6/7. To evaluate the constructive validity of the GDS-15-J, factor analysis was performed. Three factors were extracted. Cronbach's alpha reliability coefficient was .83 to the GDS-15-J scale, which indicated a high degree of internal consistency. CONCLUSION: The GDS-15-J is a clinically applicable screening instrument for depression. CLINICAL IMPLICATIONS: In this study this version of the GDS-15-J displayed excellent psychometric properties using a 6/7 cut off. Analyses suggest some items that might be removed in future studies of an abbreviated scale.