Proteinopathies Expression in Skin of Neurodegenerative Disorders

NCT06528964 | Recruiting

• 1 other identifier: 42-23
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Disease; Frontotemporal Dementia; Parkinson Disease; Atypical Parkinsonism; Amyotrophic Lateral Sclerosis; Normal Pressure Hydrocephalus

Keywords

Alpha Synuclein Pathology; Tauopathies; TDP-43 Proteinopathies; Beta-Amyloid

Outcome Measures

Primary Outcomes (1)

• Aggregation pattern of a-synuclein, amyloid-b, p-TAU and TDP-43

  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.

Study Arms (3)

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

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

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

Interventions

Immunohistochemistry and immunofluorescence DIAGNOSTIC_TEST

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; Patients with neurodegenerative disease; Patients with normal pressure hydrocephalus

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Universidad Autonoma de San Luis Potosí: lead
• Hospital Central "Dr. Ignacio Morones Prieto": collaborator

Study Sites (1)

Hospital Central Dr. Ignacio Morones Prieto

San Luis Potosí City, 78290, Mexico

RECRUITING

Related Publications (5)

• Said HM, Kaya D, Yavuz I, Dost FS, Altun ZS, Isik AT. A Comparison of Cerebrospinal Fluid Beta-Amyloid and Tau in Idiopathic Normal Pressure Hydrocephalus and Neurodegenerative Dementias. Clin Interv Aging. 2022 Apr 11;17:467-477. doi: 10.2147/CIA.S360736. eCollection 2022.

  PMID: 35431542 BACKGROUND

• Espay AJ, Da Prat GA, Dwivedi AK, Rodriguez-Porcel F, Vaughan JE, Rosso M, Devoto JL, Duker AP, Masellis M, Smith CD, Mandybur GT, Merola A, Lang AE. Deconstructing normal pressure hydrocephalus: Ventriculomegaly as early sign of neurodegeneration. Ann Neurol. 2017 Oct;82(4):503-513. doi: 10.1002/ana.25046. Epub 2017 Oct 4.

  PMID: 28892572 BACKGROUND

• Castanedo-Cazares JP, Rodriguez-Leyva I. Skin biomarkers for neurodegenerative disease: a future perspective. Neurodegener Dis Manag. 2015 Dec;5(6):465-7. doi: 10.2217/nmt.15.51. Epub 2015 Nov 30. No abstract available.

  PMID: 26619251 BACKGROUND

• Rodriguez-Leyva I, Chi-Ahumada EG, Carrizales J, Rodriguez-Violante M, Velazquez-Osuna S, Medina-Mier V, Martel-Gallegos MG, Zarazua S, Enriquez-Macias L, Castro A, Calderon-Garciduenas AL, Jimenez-Capdeville ME. Parkinson disease and progressive supranuclear palsy: protein expression in skin. Ann Clin Transl Neurol. 2016 Feb 1;3(3):191-9. doi: 10.1002/acn3.285. eCollection 2016 Mar.

  PMID: 27042679 BACKGROUND

• Golde TE, Borchelt DR, Giasson BI, Lewis J. Thinking laterally about neurodegenerative proteinopathies. J Clin Invest. 2013 May;123(5):1847-55. doi: 10.1172/JCI66029. Epub 2013 May 1.

  PMID: 23635781 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

4mm skin biopsies

MeSH Terms

Conditions

Alzheimer Disease; Frontotemporal Dementia; Parkinson Disease; Amyotrophic Lateral Sclerosis; Hydrocephalus, Normal Pressure; Synucleinopathies; Tauopathies; TDP-43 Proteinopathies; Plaque, Amyloid

Interventions

Immunohistochemistry; Fluorescent Antibody Technique

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Frontotemporal Lobar Degeneration; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Spinal Cord Diseases; Motor Neuron Disease; Neuromuscular Diseases; Hydrocephalus; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques

Central Study Contacts

Ildefonso Rodríguez-Leyva, MD PhD

CONTACT

+52 444 834 2739; ilrole@yahoo.com.mx

Cristina Monzón Tapia, MD

CONTACT

a267473@alumnos.uaslp.mx

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Neurology Service

Study Record Dates

• First Submitted: July 25, 2024
• First Posted: July 30, 2024
• Study Start: December 20, 2023
• Primary Completion (Estimated): October 25, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: December 16, 2024

Record last verified: 2024-12

Locations

ME (1)