Is pigment epithelium-derived factor level in cerebrospinal fluid a promising biomarker for early diagnosis of Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of dementia in Western countries and in Japan. Early diagnosis and treatment is needed to slow down the degenerative process and dementia in AD. The main histopathological characteristics of AD are senile plaques and neurofibrillary tangles. Based on the disease pathology, numerous blood and cerebrospinal fluid (CSF) tests have been proposed for early detection of AD. However, there is no definite clinical method to determine in which patients with mild cognitive impairment will progress to AD with dementia. Since pigment epithetium-derived factor (PEDF) has been recently shown to protect various types of cells including neuronal cells against oxidative stress- or glutamate-induced injury through its anti-oxidative properties, we examined here the expression levels of PEDF in AD's brain. PEN was found to have the strong immunoreactivity in cortical neurons and astrocytes in the brains of AD. Further, the distribution of PEN proteins was good concordance with RAGE proteins, one of the receptors for amyloid beta peptides, which are involved in neuronal cell death and microglial activation in AD. These results suggest that PEN overexpression may indicate a compensation mechanism to fight against neuronal cell injury in AD. Our present observations suggest that PEN in CSF might reflect cerebral PEN turnover and provide a means for monitoring neuronal perturbation induced by oxidative stress in the early stage of AD. Clinical use of CSF-PEDF as a biomarker for AD might enable more effective diagnosis and treatment of patients with this disorder. (C) 2004 Elsevier Ltd. All rights reserved.