Journal of Aging Research / 2011 / Article / Tab 1

Review Article

Neurobiology of Vascular Dementia

Table 1

Comparison between normal aging and neurodegenerative diseases from a molecular perspective.

ParameterNormal agingVascular dementiaAlzheimer’s diseaseOther neurodegenerative disorders

CBFDiminished with lower velocity, but with preserved dynamic adaptability [84]Diminished in parietal and frontal lobes, some authors reported also a decrement in superior temporal gyri, thalami, anterior cingulate gyri [85]Diminished only in parietal cortices and later in advanced disease in frontal lobes [86]Diminished in preoccipital and occipital regions in PD [87] and LBD [88]

VEGF -ALow basal levels produced by astrocytes [89]Upregulation of VEGF and VEGF R2 in astrocytes [90]Low serum levels and decreased secretion by peripheral immune cells [91]FTLD—associated with VEGF gene promoter polymorphism in selected populations [92]

Inflammatory cytokines
  IL-6Increased mRNA compared to young subjects [93]High blood levels, associated with high CRP may be associated with high risk [94]Positive immunoreactivity in amyloid plaques and increased concentration in AD brain, compared to age-matched subjects [95]Increased in cerebral and cerebellar cortex of Huntington patients [96]
  TNFαIncreased basal levels in aged laboratory animals with week induction injury response [97]Modulates neuronal cell loss in cerebral ischemia [98]Increased expression in AD brain, along with TNF-R1 [99]Increased in plasma [100], CSF of PD patients and in PD brains, especially in areas with greatest loss of dopaminergic neurons [101]
  TGFβ1Detected at low levels in CSF and produced in CNS at low levels by neuronal cells [102]Increased in CNS and CSF after stroke [103]Increased in areas with amyloid burden [104]CAA—directly related to amyloid vascular deposition [105]

Adhesion moleculessVCAM increased [106]sVCAM increased in atherosclerotic disease [107]; sE-selectin increased in severe cerebrovascular disease [108]sVCAM elevated in late onset AD [50]sVCAM increased in Down Syndrome [100]

ROSIncreased accumulation with aging [109]Increased in ischemia animal models and stroke patients [110]Increased: Aβ-related ROS generation and MAOS [111]Increased in PD in vitro models [112] and animal models [113]

Lipid metabolismAccumulation of ceramides and free cholesterol in cerebral cortex [114]Hypercholesterolemia is a known risk factor for VaDIncreased levels of cholesterol, and activation of cholesterol biosynthesis pathway [115]PD dementia does not correlate with apoE polymorphism or lipid profile [116]
GLUT 1Altered structure and function of GLUT-1 [117]Downregulated in prolonged hypoxia [118]Low expression in AD hippocampus and double transgenic APP/PS1 animal model Learning increases expression in mouse brain [119]Insufficiently investigated in neurodegeneration, but involved in “Glut-1 deficiency syndrome”— a treatment-resistant form of epilepsy [120]

BDNFDecreased mRNA in human plasma and hippocampus [121]Increased expression following hypoxic stress in cell cultures [122, 123] and lab animals [123]Decreased expression in hippocampus temporal and frontal cortex [124]Reduced BDNF expression in the caudate and putamen in HD patients [96] Reduced mRNA BDNF expression [125] and protein [126] in striatal neurons in PD patients

CalciumReduced homeostatic reserve [33]Involved in ischemia-induced excitotoxicity [127]Aβ disrupts Ca homeostasis in cortical neuronal cell cultures [117]Excitotoxicity and excessive Ca2+-mediated nitric oxide production are believed to contribute to the death of dopaminergic neurons in PD [118]; Huntingtin transgenic mice express mitochondrial Ca overload upon glutamate stimulation [119]

MAOS: membrane-associated oxidative stress VDCC: voltage dependent calcium channels, FTLD: frontotemporal lobar dementia, LBD: Lewy body dementia, and HD: Huntington disease.

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