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Background: Alzheimer's Disease (AD) is the most common type of dementia among older adults (Prince et al., 2015). Research has focused on specific biomarkers for AD that could contribute to early diagnosis. Levels of ADAM10, for example, are altered in people with AD, and this protein has been studied as a potential blood‐based biomarker for this disease (Elsworthy et al., 2022). Brain‐derived neurotrophic factor (BDNF), in turn, is a protective factor involved, for example, in neurotransmitter modulation, as well as in neuronal plasticity and survival (Tarassova et al., 2020). Therefore, analyzing the possible relationship between these variables is relevant to expand the knowledge of AD biomarkers. Aim: to verify whether there is a relationship between the levels of ADAM10 and BDNF among healthy older adults and individuals with AD with low educational attainment. Methods: This is a cross‐sectional study in which community‐dwelling older adults with low educational levels (n = 85) were assigned to two groups: healthy older adults (n = 37) and participants with AD (n = 48). The interview was based on a sociodemographic questionnaire and cognitive assessment (Mini‐Mental State Examination‐MMSE and the Clock Drawing Test‐CDT). Participants had their blood collected, and SDS‐PAGE and Western Blotting techniques were used to measure plasma ADAM10 levels. Results: Participants with AD were older (p<.001); had less educational attainment (p<.001); worse performance on MMSE (p<.001), and on its domains [Orientation (p<.001), attention, memory (p =.028), language(p<.001), and evocation(p<.001)]; as well as worse performance on CDT (p<.001). Also, compared to the healthy group, persons with AD had significantly higher levels of plasma ADAM10 (p =.04). No difference in BDNF levels was observed between the groups (p =.07). Correlation analyses revealed a significant correlation between ADAM10 and years of education (r = ‐.234; p =.04); MMSE total score (r = ‐.328; p =.003), and its orientation (r = ‐.224; p =.04), attention (r = ‐.278; p =.01), and evocation (r = ‐.332; p =.003) domains. BNDF was not correlated with any of the variables in this study. Conclusion: This study showed that plasma ADAM10 levels in low‐educated older adults, but not BDNF, differ between healthy and AD participants. Our results reinforce the potential role of ADAM10 as a biomarker for AD. [ABSTRACT FROM AUTHOR]

Background: ADAM10 has been investigated as a potential biomarker for Alzheimer's disease (AD) (Monteiro et al., 2021). However, most of the production in the literature comes from high‐income countries, where the population usually has high educational attainment (Mukadam et al., 2019). Evidence in the literature suggests an effect of education on cognitive performance; thus, low‐educated older adults tend to have worse scores on cognitive tests. Also, low education has been associated with an increased risk of dementia (Mukadam et al., 2019; Suemoto et al., 2022). However, little evidence is available on plasma ADAM10 levels in a sample of older adults with low educational attainment. Method: Participants were divided into three groups: Healthy (n = 33), MCI (n = 27), and AD (n = 30). Cognitive performance was assessed through MMSE and ACE‐R. SDS‐PAGE and Western‐Blotting were performed to obtain ADAM10 levels in plasma. Result: Participants were primarily female (62.1%), the mean age was 74.5 (8.2), and the average years of education was 4.6 (4.3). Healthy participants performed better than the MCI group on MMSE (p = 0.04). Compared to the healthy participants, the AD group was older (p = 0.00); had more comorbidities (p = 0.02), was prescribed more medications (p = 0.00); had worse performance both on MMSE (p = 0.00) and on ACE‐R (p = 0.003); and had higher levels of plasma ADAM10 (p = 0.033). Significant differences between MCI and AD groups for age (p = 0.01), years of education (p = 0.008), medication use (p = 0.02), and MMSE score (p = 0.00) were observed. The logistic regression analysis indicated that having lower levels of plasma ADAM10 decreases the chances of an older adult having a diagnosis of AD by 82.3% (Exp(B) = 0.177; p = 0.005; 95%CI [0.053‐0.593]). Conclusion: Our results suggested healthy low‐educated older adults had less plasma ADAM10 compared to individuals with AD. Also, despite low education, cognitive test scores differ for each group. [ABSTRACT FROM AUTHOR]

Prolonged skin exposure to ultraviolet radiation (UVR) induces premature aging in both the epidermis and the dermis. Chronic exposure to UVR induces the activation of mitogen‐activated protein kinase (MAPK) signaling pathway, activating c‐Jun, c‐Fos expression, and transcription factor of AP‐1 activating protein. AP‐1 activation results in the positive induction of matrix metalloproteinase (MMP) synthesis, which degrade skin collagen fibers. Polysaccharides from the fruit of Lycium barbarum (LBP fraction) have a range of activities and have been demonstrate to repair the photodamage. In different approaches, laser application aims to recover the aged skin without destroying the epidermis, promoting a modulation, called photobiomodulation (PBM), which leads to protein synthesis and cell proliferation, favoring tissue repair. Here we developed a topical hydrogel formulation from a polysaccharide‐rich fraction of Lycium barbarum fruits (LBP). This formulation was associated with PBM (red laser) to evaluate whether the isolated and combined treatments would reduce the UVR‐mediated photodamage in mice skin. Hairless mice were photoaged for 6 weeks and then treated singly or in combination with LBP and PBM. Histological, immunohistochemistry, and immunofluorescence analyses were used to investigate the levels of c‐Fos, c‐Jun, MMP‐1, −2, and −9, collagen I, III, and FGF2. The combined regimen inhibited UVR‐induced skin thickening, decreased the expression of c‐Fos and c‐Jun, as well as MMP‐1, −2, and −9 and concomitantly increased the levels of collagen I, III, and FGF2. The PBM in combination with LBP treatment is a promising strategy for the repair of photodamaged skin, presenting potential clinical application in skin rejuvenation. [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]

Background: Active ADAM10 is a transmembrane protein with α‐secretase function that inhibits β‐amyloid (Aβ) peptide formation, an important neuropathological agent of Alzheimer's disease (AD). In addition, persons with cognitive decline, such as Mild Cognitive Impairment (MCI), have a high conversion rate to AD. Previous studies show that the levels of active platelet ADAM10 are reduced in persons with AD dementia, compared with cognitively healthy individuals. In blood plasma the inactive and soluble form of ADAM10 is found. In this study we investigated the levels of inactive ADAM10 in plasma in order to corroborate with previous results found in platelets. Method: This study was approved by the UFSCar's Research Ethics Committee (CAAE: 02763012.0.0000.5504). Altogether, samples from 88 participants (n = 28 MCI, n = 31 AD and n = 29 controls) were analysed in this study. Blood samples were collected, plasma was separated and total protein content (15µg) was run on gel electrophoresis (SDS‐PAGE). Soluble ADAM10 (50‐55kDa) was identified by western blotting, using the anti‐ADAM10 antibody (Abcam, Ab39180) followed by the secondary antibody (Abcam, Ab97051). The serum albumin protein (66kDa) and a "young control" performed with plasma samples from a young donnor were used as endogen controls to avoid interassay biases in the densitometry analyses. Bands were measured by volume adjusted in Image Lab software and statistical analysis were performed in GraphPad Prism software. Result: Plasma levels of soluble ADAM10 are increased in persons with MCI (p = 0.0325) and AD (p = 0.0129), compared with cognitively healthy older adults. Conclusion: Plasma‐soluble ADAM10 has potential as a biomarker molecule for AD. Analyses in plasma are advantageous as they represent an easily accessible and low‐cost tool that can be used in the future by health services to aid in the early diagnosis of AD. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) may be related to changes in insulin pathways, suggesting that individuals with type 2 diabetes mellitus (T2DM) are more likely to develop AD compared to healthy individuals. Insulin plays an important role in the mechanisms related to brain activity, especially in the formation of memories. Given the similarity between insulin‐like growth factor (IGF‐1) and insulin itself, this molecule has the ability to bind to the insulin receptor, but with low affinity. In addition to the brain, IGF‐1 is present in several tissues, acting as a mediator of physiological responses related to neuronal protection against toxicity caused by glucose deprivation and oxidative stress, in addition to playing an important role in apoptosis, cell proliferation and differentiation. In vitro studies have demonstrated the potential that this protein has to decrease tau protein hyperphosphorylation, one of the pathological hallmarks of AD. Moreover, in response to neuronal damage, IGF‐1 promotes neurogenesis and synaptogenesis. Method: This is a cross‐sectional study, based on the assumptions of quantitative research, approved by the Ethics Committee of Federal University of São Carlos, SP, Brazil (CAAE: 12968413.1.0000.5504). It has been developed with a sample of 36 participants aged over 60 years, users of health services in the municipality. Specific inclusion and exclusion criteria and the MMSE and CDR cognitive assessment instruments were applied to participants from all groups. Quantification of IGF‐1 plasma levels was performed using the ELISA technique (Enzyme‐Linked Immunosorbent Assay). Result: Higher plasma levels of IGF‐1 were found in older adults with AD and concomitant T2DM when compared with older adults with diabetes (T2DM) (p = 0.0167) and healthy participants (p = 0.0003). Conclusion: The increase in IGF‐1 levels in plasma of older adults with AD+T2DM and T2DM groups may indicate an initial compensatory response against neuronal damage in the elderly with both diseases or T2DM. The findings and conclusions of the present study are exploratory, and further studies with larger sample sizes are needed to draw a firm conclusion. [ABSTRACT FROM AUTHOR]

Background: AD (Alzheimer's disease) is a progressive neurodegenerative disease characterized by extensive neuronal losses and deposits of neurofibrillary tangles and senile plaques. Patients with T2DM (type 2 diabetes mellitus) 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. Based on these findings, AD has been called by some researchers T3DM (type 3 diabetes mellitus) or cerebral diabetes. Our group has been studying peripheral biomarkers for AD since 2010. Among them, our focus is the study of ADAM10 (A Disintegrin And Metalloprotease), an α‐secretase that inhibits the formation of senile plaques and, therefore, is protective against AD. We observed that this protein is decreased in platelets and increased in plasma of elderly people with this dementia compared to cognitively healthy elderly people. Method: The participants of this research were people aged 60 or over, divided into 4 groups: participants with AD, participants with T2DM, participants with AD and concomitant presence of T2DM and cognitively unimpaired (CU) controls with regular plasma glucose levels. In this work, due to the COVID‐19 pandemic, we are presenting the results of a pilot trial carried out with data collected from 9 participants in each group. Patients' blood was collected and plasma was used in assays to determine ADAM10 levels using an ADAM10‐specific Enzyme‐Linked Immunosorbent Assay (ELISA) kit (Life Sciences, catalog number LS‐F23768). Results were confirmed using SDS‐PAGE followed by western blotting analyses with the primary antibody anti‐ADAM10 (Ab39180 rabbit, Abcam). A "young control" performed with plasma samples from a young donnor and soroalbumin bands were used as endogen controls to avoid interassay biases in the densitometry analyses. Result: Plasma ADAM10 was elevated in persons with AD and T2DM and these levels were even higher when plasma from patients with both diseases was analysed. Conclusion: This study shows a clinical impact related to a new approach that could be used in the treatment of AD, also observing the metabolic and inflammatory states of the patients. Study also contributes to a better understanding of the biology of the disease itself. [ABSTRACT FROM AUTHOR]