Alzheimer disease and Glioblastoma

Abstract

Alzheimer’s disease (AD) is characterised by progressive impairments in memory and cognitive process and contributes to 50 – 70% of dementia cases. Alzheimer’s predominantly presents in people over 65 while brain cancer incidence is similarly seen in the elderly. Glioblastoma (GBM) is the most aggressive form of primary malignant brain tumour with life expectancy only 15 months following diagnosis. A relationship between the two neurological diseases was first suggested when patients with AD were found to be less likely to die from cancer compared to AD patients who died from other diseases. Meta-analysis has confirmed that cancer patients have a 50% reduced risk of developing AD with a general consensus of inverse comorbidity. Beta amyloid exists in two main forms Aβ40 and Aβ42 and has long been at the centre of AD pathogenesis. Our preliminary data suggests it to also be present in glioma. However, the full role of beta amyloid or its associated proteins have not been fully explored in GBM.

Immortalised cell lines U87-mg (human grade IV GBM), SVGp12 (human foetal glial cell) and 1321N1 (human low-grade astrocytoma) were used throughout.

ELISA assay was able to confirm presence of both Aβ40 and Aβ42 in U87-mg, 1321N1 and SVGp12 cell lysates with no significant difference between the different cell lines. Pharmacological inhibition of beta amyloid similarly had no significant effect on cell proliferation in the glioma cell lines.

Bioinformatic exploration of beta amyloid associated genes was undertaken to identify novel targets to study in the glioma cell lines. BRCA2 and BCHE genes showed different expression in LGG and GBM compared to normal tissue. BRCA2 expression was confirmed in cell lysates by western blot with less BRCA2 in U-87mg and SVGp12 compared to 1321N1.

BRCA2 has been long implicated in other cancers, however the role BRCA2 may have in glioma brain tumours remain unknown. BRCA2 may therefore be an interesting protein for further study and a potential strategy in GBM.