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Background: The Valencian Cognitive Diseases Study (VALCODIS) provides a large cohort of cases suffering from neurodegenerative diseases causing cognitive problems in their initial phases. This cohort is being obtained from admitted patients at Cognitive Disorders Unit Hospital Universitari i Politècnic La Fe (Valencia, Spain), as a basis to contribute on the Alzheimer's disease (AD) diagnosis and prognosis research. Method: Patients who come to the Cognitive Disorders Unit at Neurology Department of Hospital La Fe can be recruited to the VALCODIS cohort after their informed consent have been obtained. Patients with moderate and severe dementia are not proposed to participate. Included patients were studied with standard analytical and neuroimaging procedures, commonly brain MR, and CSF biomarkers determination (β‐amyloid‐42, β‐amyloid‐40, p‐Tau, t‐Tau, neurofilament light chain). Patients on anticoagulation, other contraindications or not suitable for LP can be included if an amyloid brain PET can be obtained. In some patients, brain PET with FDG is also obtained. After amyloid status is assured, a detailed neuropsychological evaluation is obtained in every patient using at least MMSE, CDR, RBANS and GDS scales. Finally, blood samples were taken to determine some potential biomarkers (lipid peroxidation, lipids, proteins, microRNAs) and stored simultaneously with CSF samples. Result: A total of 1100 participants aged 50 to 80 years, who were on follow up from January 2017 to August 2022 have been included in the VALCODIS cohort. This cohort is composed by early AD patients (mild cognitive impairment (MCI), mild dementia), other dementias in their initial phases (frontotemporal dementia, Lewy body dementia, vascular dementia) and cognitively healthy persons. Also, some of MCI‐AD patients were followed‐up at 2 years to carry out a prognosis study, by means of neuropsychological evaluation and blood biomarkers. Conclusion: The VALCODIS cohort represents a valuable infrastructure describing 6‐year experience about early and specific AD diagnosis, and prognosis. This cohort will provide a large number of patients, biologically diagnosed by CSF biomarkers, as well as their demographical, clinical and biochemical data. In addition, the biological samples (blood, plasma, urine, saliva, CSF) were stored to carry out further biomarkers studies. [ABSTRACT FROM AUTHOR]

Hereditary nonpolyposis colon cancer (HNPCC) is an autosomal dominant disorder characterized by the predisposition to develop a number of cancers, especially colorectal cancer (CRC). We present a HNPCC family with CRC at age 12 years. Our observations suggest that the germline mutation of the both copies of the MLH1 gene may play a role in the early onset of CRC. [Copyright &y& Elsevier]

The incidence of early-onset colorectal cancer (EOCRC; age younger than 50 years) has been progressively increasing over the last decades globally, with causes unexplained. A distinct molecular feature of EOCRC is that compared with cases of late-onset colorectal cancer, in EOCRC cases, there is a higher incidence of Nodal Modulator 1 ( NOMO1) somatic deletions. However, the mechanisms of NOMO1 in early-onset colorectal carcinogenesis are currently unknown. In this study, we show that in 30% of EOCRCs with heterozygous deletion of NOMO1 , there were pathogenic mutations in this gene, suggesting that NOMO1 can be inactivated by deletion or mutation in EOCRC. To study the role of NOMO1 in EOCRC, CRISPR/cas9 technology was employed to generate NOMO1 knockout HCT-116 (EOCRC) and HS-5 (bone marrow) cell lines. NOMO1 loss in these cell lines did not perturb Nodal pathway signaling nor cell proliferation. Expression microarrays, RNA sequencing, and protein expression analysis by LC-IMS/MS showed that NOMO1 inactivation deregulates other signaling pathways independent of the Nodal pathway, such as epithelial-mesenchymal transition and cell migration. Significantly, NOMO1 loss increased the migration capacity of CRC cells. Additionally, a gut-specific conditional NOMO1 KO mouse model revealed no subsequent tumor development in mice. Overall, these findings suggest that NOMO1 could play a secondary role in early-onset colorectal carcinogenesis because its loss increases the migration capacity of CRC cells. Therefore, further study is warranted to explore other signalling pathways deregulated by NOMO1 loss that may play a significant role in the pathogenesis of the disease.