Proteins Present in Neurodegeneration Also in the Skin of Patients With Alzheimer’s Disease: Presented at AAN

By Masha Dowell

PHILADELPHIA -- May 6, 2014 -- Aggregates of phosphorylated tau proteins are present in the skinfolds of patients with Alzheimer’s disease, and have the potential to improve the accuracy of diagnosis, according to results of a small, randomised study presented at the 66th Annual Meeting of the American Academy of Neurology (AAN).

The presence of misfolded proteins is evidence of neurodegeneration -- and the specific biomarker can be identified in brain tissue, explained Ildefonso Rodriguez-Leyva, MD, Universidad Autonoma de San Luis Potosí, San Luis Potosí, Mexico, speaking here on April 30. The biomarker, however, is not exclusively found in the brain, he added.

Dr. Rodriguez-Leyva and colleagues performed a post-mortem study of 18 individuals, 11 of whom had been diagnosed with Alzheimer’s disease and had had all symptoms of the disease, and 7 of whom had been cognitively normal and were used as controls. Supportive imaging was available. Biopsies were all processed and analysed in a blinded fashion.

Tau protein was evidenced by means of monoclonal antibodies recognising 2 phosphorylation sites characteristic of Alzheimer’s disease. In addition, antibodies against alpha-synuclein and beta-amyloid were assayed. The immunohistochemical technique was performed in paraffin-embedded tissues and validated in parallel analyses of brain, peripheral nerve, and skin tissue from autopsies.

Sections of brain demonstrated the following: phosphorylated tau in the cortical neurons of subjects who had had Alzheimer’s disease; alpha-synuclein (Lewy bodies) in mesencephalic neurons from a subject who had had Parkinson’s disease; and amyloid plaques in the brains of subjects who had had Alzheimer’s disease. Scattered aggregates of phosphorylated tau
protein were discovered in the epidermis, peripheral-nerve terminals, dermis fibroblasts, and skin appendages of subjects who had had neurodegenerative diseases.

Aggregates of phosphorylated tau were non-detectable in control subjects.

Cytoplasmic juxtanuclear positivity was observed in the epidermis of subjects who had had Alzheimer’s disease, and in the cytoplasm of eccrine and sebaceous glands with Paired Helical Filaments (PHF) and AT8 antibodies. A significant difference (P = .007) was observed between the positive immunostaining to AT8 antibody in the skin biopsy of control-group subjects and subjects who had had Alzheimer’s disease, as determined by the Mann-Whitney U value calculator test.

Additional research is required to improve the accuracy of an Alzheimer’s disease diagnosis using a minimally invasive modality, the authors concluded.

[Presentation title: Presence of Phosphorylated Tau, alpha- Synuclein and Amyloid Protein in the Skin of Patients with Clinical Diagnosis of Alzheimer Disease. Abstract S38.003]

To read more Conference Dispatch articles, click here.