Brain Reserve Regulators in Alzheimer’s Disease

I need this, its only 14 pages for your doctor to explain to you for resisting the effects of dementia.
http://cdn.intechopen.com/pdfs/43992/InTech-Brain_reserve_regulators_in_alzheimer_s_disease.pdf

1. Introduction

Brain reserve refers to the ability of the brain to tolerate pathological changes such as those seen in AD before manifesting clinical signs and symptoms [1-3]. Neurotrophic factors (NTFs), most notably Brain Derived Neurotrophic Factor (BDNF) and its receptor Tyrosine kinase B

(TrkB), regulate synaptic plasticity and functional efficiency in adulthood [4-6] and thus may influence brain reserve. BDNF/TrkB signaling affects memory formation and retention [7,8],determines neurite length [9,1], and governs regeneration upon neuronal injury [11,12] by modifying neuronal cytoskeleton. Abnormalities in the neuronal cytoskeleton are well

documented in AD. However, how these abnormalities affect AD progression remains unclear.  In Drosophila, neurodegeneration stems directly from mutations in alpha and beta subunits of the actin capping protein (CP), demonstrating that a mutation in a gene encoding an actin

cytoskeleton regulator can lead to demise of neurons [13]. Further, a causative role for actin cytoskeleton abnormalities in neurotoxicity has been documented in a Drosophila tauopathy model [14]. Important evidence that cytoskeletal abnormalities are critically involved in the pathogenesis of neurodegeneration stems from the studies demonstrating the effect of apolipoprotein E isoform ε4 (ApoE ε4), the well-documented genetic risk factor for the most common form of AD, late-onset AD [15], on neuronal cytoskeleton. In the United States, the ApoEε4 allele occurs in 

60% of AD patients. ApoEε4 inhibits neurite outgrowth in cultured neuronal cells[16] and correlates with the simplification of dendritic branching patterns in the brains of AD patients [17]. ApoE ε4 dose inversely correlates with dendritic spine density in dentate gyrusneurons of both AD and aged normal controls [18]. Overexpression and neuron-specificproteolytic cleavage of ApoEε4 result in tau hyperphosphorylation in neurons of transgenic mice, suggesting a role of ApoEε4 in cytoskeletal destabilization and the development of AD-related neuronal deficits [19,20]. Humanized ApoE ε4 knock-in homozygous transgenic mice