Role of the MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer disease

Speaker : 高家民                              Time: 2005/11/16 13:10-14:00

Commentator: 黃朝慶醫師                      Place: Room 601

Abstract:

In the elderly, the main cause of dementia is Alzheimer disease.  Alois Alzheimer observed that there were neuronal and vascular lesions in the brain of an Alzheimer disease patient in 1906. For century, it is unclear what the relationship between the two lesions is.  Recently, more and more evidences show that the dysfunction of neurovascular unit may cause neuronal lesions.  The neurovascular dysregulation could reduce blood flow, compromise angiogenesis, lead to insufficient clearance of Ab and subsequently result in neurovascular inflammation.  Finally, synapses and neurons are damaged and loss².  Based on these information, the authors investigated the cause of cerevascular alterations in Alzheimer disease.  Firstly, they profiled the transcription of human brain endothelial cells isolated from Alzheimer disease patients.  They showed that the mesenchyme homeobox 2 (MEOX2) gene, which affects vascular differentiation, was downregulated in Alzheimer disease patients.  Secondly, using gene silencing and restoring, they found that restoring expression of the gene stimulated angiogenesis, increased the neuron toxin Ab clearance receptor (LRP) , and suppressed the apoptosis-related transcription factor AFX1.  When exposed to the powerful angiogenic stimulus, the heterozygous (Meox2^+/-) mice did not increase the cerebral capillary numbers and had a compromised Ab clearance due to reduced LRP level.  Thus, the authors suggested that the MEOX2 gene is a key player in neurovascular dysfunction in Alzheimer disease¹.

References:

1.         Wu, Z. et al. Role of the MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer disease. Nat Med 11, 959-65 (2005).

2.         Zlokovic, B.V. Neurovascular mechanisms of Alzheimer's neurodegeneration. Trends Neurosci 28, 202-8 (2005).