S ummary HLA-A, B, C, and DR antigens were investigated in a total group of 76 leprosy patients, classified according to the system of Ridley and Jopling in 30 IT and 46 LL individuals. A group of 100 healthy subjects were included for comparison. Patients and controls were all Mexican Mestizos born and inhabitants of Mexico. Typing of blood group systems was also performed. All IT patients showed a positive lepromin skin test, while all LL patients were negative to the specific antigen. The distribution of red-ceIl antigens was similar in both groups. The results of HLA typing demonstrated a significant association of DR3 with the tuberculoid type (X2 = 11•85; p=0'0007; pc = 0•04). The RR value for DR3 carriers was 4•93 and the EF was 0•24. It is concluded that a Class 11linked susceptibility gene plays an important role in the expression of tuberculoid leprosy. This gene is closely linked to DR3 in the Mexican population. A considerable number of studies have been reported looking for an association between leprosy and gene products of the major histocompatibility complex (MHC) in humans. Firstly, concerning the HLA class I antigens, 1-1 0 and later to the molecules belonging to the 0 region.I J-1 6 An analysis of the published results up to 1983 has been reviewed by Serjeantson et al. J7 Even though technical problems in HLA typing were sometimes evident, and the control group matching or the disease classification were not strictly considered, and a consistent association between A or B antigens could not be established from population studies, inheritance of HLA haplotypes in fa milies provided evidence of the participation of HLA genes in the sus c eptibility to leprosy. 1 7-2 1 Typing of class II products, which include HLA DR, DQ and DP antigens, clearly showed the relationship between DR antigens and tuberculoid leprosyll-1 6 in random population as well as in fa milies. Leprosy in Mexico is an endemic disease with an incidence of 21/100,000 inhabitants and the patients are mainly located in the central plateau and the west area of the country .22 The most common type of leprosy according to the classification of Ridley and Jopling23 is the lepromatous fo rm; 62% of the cases are LL and BL, 23% are BB and only 15% are IT and BT.2 4 For this reason, the first group we studied in 19732 looking for genetic factors was of LL patients. At that time, we fo und a decrease of A2 and A3, but only 8 antigens were explored. In a fu rther work done by us in

Background: Disturbances in the autophagy/endolysosomal systems are proposed as early signatures of Alzheimer’s disease (AD). However, few studies are available concerning autophagy gene expression in AD patients. Objective: To explore the differential expression of classical genes involved in the autophagy pathway, among them a less characterized one, DEF8 (Differentially expressed in FDCP 8), initially considered a Rubicon family member, in peripheral blood mononuclear cells (PBMCs) from individuals with mild cognitive impairment (MCI) and probable AD (pAD) and correlate the results with the expression of DEF8 in the brain of 5xFAD mice. Method: By real-time PCR and flow cytometry, we evaluated autophagy genes levels in PBMCs from MCI and pAD patients. We evaluated DEF8 levels and its localization in brain samples of the 5xFAD mice by real-time PCR, western blot, and immunofluorescence. Results: Transcriptional levels of DEF8 were significantly reduced in PBMCs of MCI and pAD patients compared with healthy donors, correlating with the MoCA and MoCA-MIS cognitive tests scores. DEF8 protein levels were increased in lymphocytes from MCI but not pAD, compared to controls. In the case of brain samples from 5xFAD mice, we observed a reduced mRNA expression and augmented protein levels in 5xFAD compared to age-matched wild-type mice. DEF8 presented a neuronal localization. Conclusion: DEF8, a protein proposed to act at the final step of the autophagy/endolysosomal pathway, is differentially expressed in PBMCs of MCI and pAD and neurons of 5xFAD mice. These results suggest a potential role for DEF8 in the pathophysiology of AD.

Background: Amyloid-β peptide (Aβ) deposition in Alzheimer’s disease (AD) is due to an imbalance in its production/clearance rate. Aβ is transported across the blood-brain barrier by LRP1 and P-gp as efflux transporters and RAGE as influx transporter. Vitamin D deficit and polymorphisms of the vitamin D receptor (VDR) gene are associated with high prevalence of mild cognitive impairment (MCI) and AD. Further, vitamin D promotes the expression of LRP1 and P-gp in AD-animal model brains. Objective: To associate VDR polymorphisms Apa I (rs7975232), Taq I (rs731236), and Fok I (rs2228570) with the risk of developing MCI in a Chilean population, and to evaluate the relationship of these polymorphisms to the expression of VDR and Aβ-transporters in peripheral blood mononuclear cells (PBMCs). Methods: VDR polymorphisms Apa I, Taq I, and Fok I were determined in 128 healthy controls (HC) and 66 MCI patients. mRNA levels of VDR and Aβ-transporters were evaluated in subgroups by qPCR. Results: Alleles A of Apa I and C of Taq I were associated with a lower risk of MCI. HC with the Apa I AA genotype had higher mRNA levels of P-gp and LRP1, while the expression of VDR and RAGE were higher in MCI patients and HC. For Fok I, the TC genotype was associated with lower expression levels of Aβ-transporters in both groups. Conclusion: We propose that the response to vitamin D treatment will depend on VDR polymorphisms, being more efficient in carriers of protective alleles of Apa I polymorphism.

Background LRP1 and P‐gp are the major efflux transporters of β‐amyloid peptide (Aβ) across the blood brain barrier and the expression of both transporters is mediated by the vitamin D receptor (VDR). Three single nucleotide VDR polymorphisms (SNPs) Taq I, Apa I and Fok I have been related to mild cognitive impairment (MCI); however, their functional effect on the expression of VDR and its target genes remains unclear. Method 76 MCI patients and 133 elderly volunteers were cognitively screened with the Montreal Cognitive assessment (MoCA) and MoCA‐MIS after signing an informed consent approved by the Ethics Committee of Hospital Clínico Unversidad de Chile. The VDR SNPs Apa (rs7975232), Taq (rs731236) and Fok I (rs2228570) were determined by TaqMan SNP genotyping assay. mRNA levels of VDR, LRP1 and P‐gp were evaluated by qPCR. Result The C and T alleles of Apa I and Taq I respectively were more frequent in the MCI (p < 0.05); additionally the odds ratio analysis (OR) was significant for both alleles (C allele OR: 1.5 p = 0.049; T allele OR: 1.89, p = 0.0044). There were no significant differences for Fok I polymorphism between the groups. Furthermore, the homozygous CC of Apa I had significantly lower mRNA levels of P‐gp and VDR than the homozygous AA and heterozygous AC (p < 0.05). The carriers of one copy of the C allele (TC) of Fok I had lower mRNA levels of VDR and of both transporters than the homozygous TT (p < 0.005). Conclusion The C and T alleles of Apa I and Taq I respectively might be risk alleles for MCI, as reported in other populations. In addition, we found that SNPs of the VDR gene are related to the decrease of the mRNA levels of the Aβ transporter P‐gp and the transcription factor VDR.