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Background: The kidney-brain crosstalk has been involved in Alzheimer's disease (AD) with the mechanism remaining unclear. The anti-aging factor Klotho was reported to attenuate both kidney injury and AD pathologies. Objective: To investigate whether plasma Klotho participated in kidney-brain crosstalk in AD. Methods: We enrolled 33 PiB-PET-positive AD patients and 33 amyloid-β (Aβ)-negative age- and sex-matched cognitively normal (CN) controls from the Chongqing Ageing & Dementia Study (CADS). The levels of plasma Klotho, Aβ, and tau in the cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay. Results: We found higher plasma Klotho and lower estimated glomerular filtration rate (eGFR) levels in AD patients compared with CN. The eGFR was positively associated with Aβ42, Aβ40 levels in CSF and negatively associated with CSF T-tau levels. Plasma Klotho levels were both negatively correlated with CSF Aβ42 and eGFR. Mediation analysis showed that plasma Klotho mediated 24.96% of the association between eGFR and CSF Aβ42. Conclusion: Renal function impacts brain Aβ metabolism via the kidney-brain crosstalk, in which the plasma Klotho may be involved as a mediator. Targeting Klotho to regulate the kidney-brain crosstalk provides potential therapeutic approaches for AD. [ABSTRACT FROM AUTHOR]

Background: The dysregulation of lipid metabolism plays an important role in the pathogenesis of Alzheimer's disease (AD). Liver-type fatty acid-binding protein (L-FABP, also known as FABP1) is critical for fatty acid transport and may be involved in AD.Objective: To investigate whether the FABP1 level is altered in patients with AD, and its associations with levels of amyloid-β (Aβ) and tau in the plasma and cerebrospinal fluid (CSF).Methods: A cross-sectional study was conducted in a Chinese cohort consisting of 39 cognitively normal controls and 47 patients with AD. The levels of FABP1 in plasma, and Aβ and tau in CSF, were measured by enzyme-linked immunosorbent assay (ELISA). A single-molecule array (SIMOA) was used to detect plasma Aβ levels.Results: The level of plasma FABP1 was significantly elevated in the AD group (p = 0.0109). Further analysis showed a positive correlation of FABP1 with CSF total tau (t-tau) and phosphorylated tau (p-tau) levels. Besides, plasma FABP1/Aβ42 (AUC = 0.6794, p = 0.0071) and FABP1/t-tau (AUC = 0.7168, p = 0.0011) showed fair diagnostic efficacy for AD. When combined with other common AD biomarkers including plasma Aβ42, Aβ40, and t-tau, both FABP1/Aβ42 and FABP1/t-tau showed better diagnostic efficacy than using these biomarkers alone. Among all AUC analyses, the combination of plasma FABP1/t-tau and Aβ42 had the highest diagnostic value (AUC = 0.8075, p < 0.0001).Conclusion: These findings indicate that FABP1 may play a role in AD pathogenesis and be worthy of further investigation in the future. [ABSTRACT FROM AUTHOR]

Background: The G protein-coupled receptor P2RY2 protein of the purinergic receptor family is involved in the pathogenesis of Alzheimer's disease (AD). Naturally occurring antibodies against P2RY2 (NAbs-P2RY2) are present in human plasma, with their clinical relevance in AD unknown.Objective: To explore the alteration of NAbs-P2RY2 in AD patients and its associations with biomarkers and cognition of AD patients.Methods: The levels of naturally occurring antibodies against the four extracellular domains of P2RY2 (NAbs-P2RY2-1, NAbs-P2RY2-2, NAbs-P2RY2-3, and NAbs-P2RY2-4) were measured in the plasma of 55 AD patients, 28 non-AD dementia patients, and 70 cognitively normal participants. The correlations of autoantibody levels with cognitive scale scores, AD plasma biomarkers, and brain amyloid burden were examined.Results: NAbs-P2RY2-1, NAbs-P2RY2-3, and NAbs-P2RY2-4 were reduced in AD patients. Plasma levels of NAbs-P2RY2-2 and NAbs-P2RY2-3 levels were positively associated with cognitive and functional performances. Among these antibodies, plasma NAbs-P2RY2-2 levels were positively associated with plasma amyloid-β 42 levels. While plasma NAbs-P2RY2-3 levels were negatively associated with brain amyloid burden in AD patients.Conclusion: These findings indicate an alteration of humoral immunity against P2RY2 in AD patients. Further mechanistical investigations are needed to reveal the role of NAbs-P2RY2 in the pathogenesis of AD. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that monocytes can phagocytize the tau protein, which may ameliorate tau-type pathology in Alzheimer's disease (AD). However, there are few clinical studies on the relationship between monocytes and tau-type pathology in AD patients.Objective: We aimed to explore changes in peripheral monocytes and their association with tau protein in AD patients.Methods: A total of 127 clinically diagnosed AD patients and 100 age- and sex-matched cognitively normal controls were recruited for analysis of the correlation of plasma tau levels with the blood monocyte count. Cerebrospinal fluid (CSF) samples from 46 AD patients and 88 controls were further collected to analyze the correlation of CSF tau and amyloid-β (Aβ) levels with the blood monocyte count. 105 clinically diagnosed mild cognitive impairment (MCI) patients and 149 age- and sex-matched cognitively normal controls were recruited from another cohort for verification.Results: Compared to normal controls, AD patients showed a significant reduction in the blood monocyte count. In addition, the monocyte count of AD patients was negatively correlated with CSF t-tau and p-tau levels but not with plasma tau levels. In normal people, monocyte count lack correlation with tau levels both in plasma and CSF. Monocyte count were not correlated with CSF Aβ levels in either group but were negatively correlated with CSF tau/Aβ42 levels in the AD group. We had further verified the correlations of monocyte count with CSF tau levels in another cohort.Conclusion: This study suggests that monocytes may play an important role in the clearance of tau protein in the brain. [ABSTRACT FROM AUTHOR]

Background: Few studies of gene variants that affect estrogen activity investigate their association with age at onset of Alzheimer's disease (AD) in women of different ethnicities. We investigated the influence of ESR2 polymorphisms on age at onset of AD in a multiethnic cohort of women. Objectives: To determine whether gene variants would affect risk for AD differently in women of different population ancestries. Methods: Among 1,686 women participating in the Washington Heights Inwood Columbia Aging Project (WHICAP), association with risk for AD was assessed for 20 ESR2 single-nucleotide polymorphisms (SNPs) using multivariate logistic regression, adjusting for age at time of study enrollment, presence of an APOE ε4 allele, years of education, and body mass index. Results: Increased risk for AD was associated with four ESR2 SNPs in women of predominantly Caucasian AIMS-defined ancestry: rs944045, rs1256062, rs10144225, and rs2274705 (OR range 1.6-1.9, empiric p-value range 0.002-0.004). A separate SNP (rs10137185) was associated with decreased risk for AD in women who identified themselves as Black (OR 0.6, 95% CI = 0.4-0.9). When vascular risk factors were included in the model, a separate SNP (rs1256059) was associated with increased risk for AD in women of admixed/Hispanic ancestry (OR 1.5, 95% CI = 1.1-2.4). Conclusions: ESR2 polymorphisms affect risk for AD in women, and risk alleles vary by AIMs-defined ancestry and self-identified ethnicity. These effects are possibly due to different linkage disequilibrium patterns or differences in comorbid risk factors mediating SNP effect on risk for AD by group. [ABSTRACT FROM AUTHOR]