Proteinopathies Expression in Skin of Neurodegenerative Disorders

Alzheimer's disease is the main cause of neurodegenerative dementia and represents a high degree of morbidity and mortality among the patients who have it, causing a great economic impact in health systems. In general population the second cause of neurodegenerative dementia is frontotemporal lobe dementia and it's also the first cause of dementia in patients under 65 years old. Neurodegenerative diseases have been associated with the deposit of abnormal aggregated proteins like alpha-synuclein, amyloid-beta, phosphorylated tau and TAR DNA binding protein 43 in brain tissue. Similar deposits of a-synuclein, p-TAU and TDP-43 have been identified through immunohistochemistry and immunofluorescence in skin biopsies. Main objective: Compare the aggregation pattern between the different proteinopathies (a-synuclein, amyloid-b, p-TAU and TDP-43) with immunohistochemistry in skin biopsies of patients with Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism, amyotrophic lateral sclerosis and normal pressure hydrocephalus vs control subjects. Study design: this will be an observational, transversal and comparative analysis study. Inclusion criteria: patients, men and women, 45 and older diagnosed with Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism, amyotrophic lateral sclerosis or normal pressure hydrocephalus will be recruited for sampling with skin biopsy. Healthy control subjects will be men or women similar in age to the patients that don't have any personal or family history of a neurodegenerative disease and that are not related by blood to the patients in this study. Sample size calculation and statistical analysis: All the patients that meet the inclusion criteria and accept the consent form, from the neurology department of Hospital Central Dr Ignacio Morones Prieto, will be recruited for one year. A descriptive analysis will be carried out with frequencies and percentages for categorical variables, for continuous variables central tendency and dispersion analysis, the normality of the data will be evaluated using the Kolmogorov-Smirnov or Shapiro-Wilk test as appropriate. In case the data ha a normal distribution, it will be analyzed with the ANOVA test followed by Tukey and in the case the data doesn't have a normal distribution the analysis will be made with Kruskal Wallis followed by Mann Whitney U.