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Introduction: Low educational attainment is a potential risk factor for Alzheimer's disease (AD) development. Alpha-secretase ADAM10 plays a central role in AD pathology, attenuating the formation of beta-amyloid peptides and, therefore, their aggregation into senile plaques. This study seeks to investigate ADAM10 as a blood-based biomarker in mild cognitive impairment (MCI) and AD in a diverse group of community-dwelling older adults, focusing on those with limited educational attainment. Methods: Participants were recruited from public health services. Cognition was evaluated using Mini-Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination – Revised (ACE-R) batteries. Blood samples were collected to analyze plasma ADAM10 levels. A logistic regression was conducted to verify the influence of plasma ADAM10 on the AD diagnosis. Results: Significant differences in age, years of education, prescribed medications, and cognitive test scores were found between the MCI and AD groups. Regarding cognitive performance, both ACE-R and MMSE scores displayed significant differences between groups, with post hoc analyses highlighting these distinctions, particularly between AD and cognitively unimpaired individuals. Elevated plasma ADAM10 levels were associated with a 4.5-fold increase in the likelihood of a diagnosis of MCI and a 5.9-fold increase in the likelihood of a diagnosis of AD. These findings suggest ADAM10 levels in plasma as a valuable biomarker for assessing cognitive status in older individuals with low education attainment. Conclusion: This study underscores the potential utility of plasma ADAM10 levels as a blood-based biomarker for cognitive status, especially in individuals with low educational backgrounds, shedding light on their relevance in AD development and diagnosis. [ABSTRACT FROM AUTHOR]

To identify which factors are associated with cognitive frailty (CF), as well as the impact of CF on the incidence of dementia and mortality. A systematic review with meta-analysis was carried out using papers that enrolled a total of 75,379 participants and were published up to January 2020. Of the 558 identified records, 28 studies met the inclusion criteria and were included in the review. The meta-analysis of cross-sectional studies showed that CF has a significant association of having an older age and a history of falls. In longitudinal studies, the analysis showed a significant increase in risk of mortality and dementia for those with CF. This is the first systematic review and meta-analysis on CF, which addressed a wide variety of factors associated with the theme and which pointed out some as a potential target for prevention or management with different interventions or treatments, showing the clinical importance of its identification in the most vulnerable and susceptible groups. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a gradual and progressive neurodegenerative disease characterized by predominant cortical atrophy in the medial temporal lobe. Since the results of the Rotterdam study in 1992, it has been known that type 2 diabetes mellitus (T2DM) increases the risk of dementia. Persons with T2DM have structural brain changes and cognitive impairment, with a high risk of developing AD. These data suggest that insulin may play a key role in brain activity and memory formation. The objective of this study was to verify if there are alterations in the levels of proteins of the insulin pathway in cognitively healthy individuals, with AD, with T2DM and with the concomitant presence of AD and T2DM. Method: The study was approved by the UFSCar's ethics committee (CAAE: 31634720.9.0000.5504) and recruited participants aged 60 years or older. The AD diagnosis was obtained using the criteria of the National Institute Aging Alzheimer's Association (NIA/AA). T2DM was defined as self‐reported use of oral antidiabetic drugs. Specific inclusion and exclusion criteria and cognitive assessment of the MMSE and CDR were applied to all participants. Plasma was collected by venepuncture and protein levels of ISNR, IRS1, Akt1, PI3KCD, MAPK1, MAPK8, PTP1B and IDE (Life‐Span Biosciences) were analysed using ELISA (Enzyme Enzyme‐Linked Immunosorbent Assay). Result: Several proteins of the insulin pathway were found to be significantly different among patients with AD, T2DM and AD+T2DM, compared with healthy controls (figure 1), reinforcing the strong correlation between T2DM and AD. Main alterations were found for INSR, IRS1, Akt1, PIK3, MAPK, PTP1b and IDE among healthy participants and those with AD+T2DM. Conclusion: The peripheral alterations found in the levels of insulin pathway proteins confirm the possible relationship between T2DM and AD and reinforce the importance of the insulin signalling pathways, as they can play a fundamental role in AD. The clinical impact of this study is related to a new approach that could be used in the treatment of this type of dementia, also observing the metabolic and inflammatory states of the patients, in addition to contributing to a better understanding of the biology of the disease itself. [ABSTRACT FROM AUTHOR]

Background: The ε4 allele of APOE is the strongest genetic risk for sporadic late‐onset Alzheimer's disease (AD), and is associated with an increase in the levels of β‐amyloid (Aβ) deposition. The main α‐secretase that inhibits the Aβ deposition is the ADAM10, which is altered in the blood and cerebrospinal fluid (CSF) of older adults with AD. Method: To assess whether the levels of ADAM10 forms are altered in CSF of AD and non‐dementia control (NDC) individuals with different APOE genotype, we analysed a total of 13 samples from NDC (mean age = 66.3 ±9.8; T‐tau = 305 ±135 ng/L; Aβ42 = 780 ±253 ng/L) and 41 from AD (mean age 77.0 ±6.2; T‐tau = 845 ±356.1 ng/L; Aβ42 = 456 ± 66 ng/L), subdivided into NDC APOE ε3/ε3 (n = 8), NDC APOE ε3/ε4 (n = 5), AD APOE ε3/ε3 (n = 13), AD APOE ε3/ε4 (n = 14) and AD APOE ε4/ε4 (n = 14). ADAM10 was characterized in human CSF samples by western blotting. Result: An antibody raised against to the ectodomain region of ADAM10, common to all species, recognized three bands, which might be the proADAM10 (immature form retaining the prodomain), ADAM10f (mature unprocessed full‐length form) and sADAM10 (truncated fragment). Regarding proADAM10, no differences were found among NDC with different APOE genotype. However, the AD APOE ε4/ε4 showed a reduction, which was significantly lower than AD APOE ε3/ε3 (p = 0.0011), NDC APOE ε3/ε3 (p = 0.0460) and NDC APOE ε3/ε3 (p = 0.0012), suggesting the impact of being homozygous for APOE ε4 allele on proADAM10 levels. In the ADAM10f and sADAM10, we observed similar findings. For both species of protein, AD groups carriers of APOE ε4 allele, that is, AD APOE ε3/ε4 and AD APOE ε4/ε4, presented significant lower levels of ADAM10f compared with both non‐carriers subgroups (AD APOE ε3/ε3 and NDC APOE ε3/ε3). Conclusion: The results indicated that being a carrier of the APOE ε4 allele and having developed AD are associated with lower levels of ADAM10f and sADAM10. This study contributes to a better understanding the impact of apoE on the disease. [ABSTRACT FROM AUTHOR]