Proteinopathies Expression in Skin of Neurodegenerative Disorders

December 13, 2024 updated by: Ildefonso Rodriguez-Leyva, Universidad Autonoma de San Luis Potosí

Expression of Proteinopathies in Skin Biopsies of Patients With Neurodegenerative Disorders

The goal of this observational study is to compare the aggregation pattern of proteinopathies (alpha-synuclein, amyloid-beta, phosphorylated tau and transactive response DNA -binding protein 43 [TDP43]) in skin biopsies of patients with a neurodegenerative disease like Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism, amyotrophic lateral sclerosis or normal pressure hydrocephalus. The main question it aims to answer is:

  • Is there a specific pattern of aggregation of proteinopathies in skin biopsies in each neurodegenerative disease in comparison to healthy control subjects?

Skin biopsies will be analyzed using immunohistochemistry and immunofluorescence for detection of alpha-synuclein, amyloid-beta, phosphorylated tau and TAR DNA binding protein 43, and the aggregation patterns will be compared between patients with a neurodegenerative disease vs patient with normal pressure hydrocephalus vs healthy control subjects.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Ildefonso Rodríguez-Leyva, MD PhD
  • Phone Number: +52 444 834 2739
  • Email: ilrole@yahoo.com.mx

Study Contact Backup

Study Locations

  • Mexico
      • San Luis Potosí, Mexico, 78290
        • Recruiting
        • Hospital Central Dr. Ignacio Morones Prieto
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Cristina Monzón Tapia, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The patients and controls that meet the eligibility criteria will be recruited from the neurology department consult from the Hospital Central Dr Ignacio Morones Prieto

Description

Inclusion Criteria for patients:

  • Patients 45 years and older
  • Men and women
  • Patients diagnosed with Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism, amyotrophic lateral sclerosis or normal pressure hydrocephalus
  • Patients that voluntarily accept to participate in the study and accept the consent form

Inclusion Criteria healthy control subjects:

  • People 45 years and older
  • Men and women
  • Subjects can be related to a patient but not by blood (for example spouse of a patient)
  • Subjects don't have direct family history of a neurodegenerative control
  • Subjects don't have any clinical findings suggesting dementia
  • Subjects voluntarily accept to participate in the study and accept the consent form

Exclusion Criteria:

  • Patients or controls that have a personal history of cerebrovascular disease, psychiatric disease, post traumatic dementia or HIV related dementia
  • Patients in which the diagnosis is not clear or hasn't been confirmed
  • Patients or controls that have a neuroinfection
  • Patients or controls that a diagnosed skin disease
  • Patients that have an "atypical" presentation of the disease
  • Patients or controls that have diagnosis of a coagulopathy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients with neurodegenerative disease
Patients diagnosed with either Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism or amyotrophic lateral sclerosis.
Diagnostic test: Immunohistochemistry and immunofluorescence
Skin biopsies will be analyzed using immunohistochemistry and immunofluorescence to detect the presence of aggregated a-synuclein, amyloid-b, p-TAU and TDP-43.
Patients with normal pressure hydrocephalus
Patients diagnosed with normal pressure hydrocephalus, because of their clinical presentation (acute or subacute gait abnormalities, memory loss or personality changes and urinary incontinence) with radiological confirmation of ventriculomegaly and normal cerebrospinal fluid opening pressure.
Diagnostic test: Immunohistochemistry and immunofluorescence
Skin biopsies will be analyzed using immunohistochemistry and immunofluorescence to detect the presence of aggregated a-synuclein, amyloid-b, p-TAU and TDP-43.
Healthy control subjects
Person, men or women, above 45 years old, that don't have history of family or personal neurodegenerative disease.
Diagnostic test: Immunohistochemistry and immunofluorescence
Skin biopsies will be analyzed using immunohistochemistry and immunofluorescence to detect the presence of aggregated a-synuclein, amyloid-b, p-TAU and TDP-43.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Aggregation pattern of a-synuclein, amyloid-b, p-TAU and TDP-43
Time Frame: Each patient will be recruited and sampled the same day of the evaluation which will take about 1 hour. The final report it takes a frame time around two years.
The detection of each proteinopathy will be compared between each of them in every patient and compared to healthy control subjects.
Each patient will be recruited and sampled the same day of the evaluation which will take about 1 hour. The final report it takes a frame time around two years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidad Autonoma de San Luis Potosí

Collaborators

Hospital Central "Dr. Ignacio Morones Prieto"

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 20, 2023

Primary Completion (Estimated)

October 25, 2026

Study Completion (Estimated)

November 1, 2026

Study Registration Dates

First Submitted

July 25, 2024

First Submitted That Met QC Criteria

July 29, 2024

First Posted (Actual)

July 30, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

December 13, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 42-23

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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