Increased Lamin A expression and heterochromatin changes in the hippocampus at early Alzheimer’s disease stages (1849)

  1. Ildefonso Rodriguez-Leyva 1
  2. Laura Gil 5
  3. Erika Chi-Ahumada 2
  4. Sandra Niño 2
  5. Carmen Guerrero-Marquez 3
  6. Ana Belen Rebolledo-Poves 3
  7. Jose Antonio Arias 4
  8. Ma. Esther Jimenez-Capdeville 6
  1. 1 Facultad de Medicina, Universidad Autonoma de San Luis Potosi
  2. 2 Facultad de Medicina, UASLP
  3. 3 Brain’s Bank, Hospital Universitario Fundación Alcorcón
  4. 4 Universidad Alfonso X el Sabio
    info

    Universidad Alfonso X el Sabio

    Villanueva de la Cañada, España

    ROR https://ror.org/054ewwr15

  5. 5 Genetics Department, Universidad Alfonso X el Sabio
  6. 6 biochemestry, Facultad de Medicina, UASLP
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Revista:
Neurology

ISSN: 0028-3878,  1526-632X

Año de publicación: 2020

Volumen: 94

Número: 15 Supplement

Tipo: Artículo

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Otras publicaciones en: Neurology

Resumen

Objective: To compare the presence of Lamin A, p-Tau and the heterochromatin marker H4K20me3 in hippocampal sections from control and AD brains.Background: It has been proposed that Alzheimer’s disease (AD) is an aging-associated laminopathy. In Drosophila melanogaster , structural Lamin B dysfunction mediates neurodegeneration linked to Tau protein. In human cells, Lamin A interacts with genome through lamin-associated domains (LADs) and regulates gene expression, but it’s poorly expressed in neurons, and its participation in AD is unknown.Design/Methods: Paraffin sections obtained from control and AD brains at stages I–II, III–IV, and V–VI were processed for immunohistochemistry and immunofluorescence. The following nuclear, nucleolar, and heterochromatin specific markers were tested in the hippocampal CA1 and CA3 regions: p-Tau, Lamin A, B23 (nucleophosmin) and H4K20me3.Results: At initial AD stages(I–II), p-Tau leaves neuronal nuclei and accumulates in the cytoplasm leading to neurofibrillary tangles (AD stages III–VI). Simultaneously, a marked increase of Lamin A expression and H4K20me3 in LADs is observed in hippocampal pyramidal neurons.Conclusions: Anomalous Lamin A expression and epigenetic changes that modify the heterochromatin structure are critical events at the beginning of neurodegeneration.Disclosure: Dr. Rodriguez-Leyva has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Teva, UCB. Dr. Gil has nothing to disclose. Dr. Chi has nothing to disclose. Dr. Nino has nothing to disclose. Dr. Guerrero-Marquez has nothing to disclose. Dr. Rebolledo-Poves has nothing to disclose. Dr. Arias has nothing to disclose. Dr. Jimenez-Capdeville has nothing to disclose.