Positron emission tomographic studies of aging and Alzheimer disease. AJNR Am J Neuroradiol 4:568-571

American Journal of Neuroradiology (Impact Factor: 3.68). 05/1983; 4(3):568-71.
Source: PubMed

ABSTRACT In this study the positron emission tomographic (PET)-18F-2-deoxy-2-fluoro-D-glucose (FDG) technique was used to study both normal aging and senile dementia. The results derived from 15 young normal subjects (mean age, 26 +/- 5 years) and 22 elderly normal subjects (mean age, 66 +/- 7 years) failed to indicate significant metabolic changes associated with age. A group of 24 patients with senile dementia (mean age, 73 +/- 7 years) showed consistent diminutions in regional glucose use relative to the elderly normals. Across all brain regions the diminutions were 17%-24%. There were also significant correlations between the measures of glucose use and the measures of cognitive functioning. Discriminant function classification analysis results indicate that better than 80% classification accuracy can be achieved for individual PET measures. These data suggest a possible future diagnostic use of PET in senile dementia.

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    • "Early studies utilizing PET indicated that brain metabolism throughout the cortex in AD patients is significantly lower than cortical metabolism in normal subjects [11] [12]. Clinical data from PET studies have shown which areas of the brain are mostly affected by mild and moderate AD, such as the posterior cingulate cortex, parietotemporal cortex, and prefrontal association cortices [13]. "
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    ABSTRACT: Hypometabolism is a hallmark of Alzheimer's disease (AD) and implicates a mitochondrial role in the neuropathology associated with AD. Mitochondrial amyloid-beta (Aβ) accumulation precedes extracellular Aβ deposition. In addition to increasing oxidative stress, Aβ has been shown to directly inhibit mitochondrial enzymes. Inhibition of mitochondrial enzymes as a result of oxidative damage or Aβ interaction perpetuates oxidative stress and leads to a hypometabolic state. Additionally, Aβ has also been shown to interact with cyclophilin D, a component of the mitochondrial permeability transition pore, which may promote cell death. Therefore, ample evidence exists indicating that the mitochondrion plays a vital role in the pathophysiology observed in AD.
    03/2011; 2011:104545. DOI:10.4061/2011/104545
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    • "Identification of the molecular mechanisms underlying these processes is essential for the development of rational therapeutics to treat or prevent this disorder. Numerous studies have linked impaired energy metabolism to AD (Craft and Watson, 2004; de Leon et al., 1983; Hoyer, 2004; Rapoport, 1999a, b; Steen et al., 2005). Studies of postmortem AD brains have also shown increased BACE1 levels compared with age-matched, nondemented controls (Fukumoto et al., 2002; Holsinger et al., 2002; Li et al., 2004; Sennvik et al., 2004; Tyler et al., 2002; Yang et al., 2003; Zhao et al., 2007). "
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    ABSTRACT: beta-site APP cleaving enzyme-1 (BACE1), the rate-limiting enzyme for beta-amyloid (Abeta) production, is elevated in Alzheimer's disease (AD). Here, we show that energy deprivation induces phosphorylation of the translation initiation factor eIF2alpha (eIF2alpha-P), which increases the translation of BACE1. Salubrinal, an inhibitor of eIF2alpha-P phosphatase PP1c, directly increases BACE1 and elevates Abeta production in primary neurons. Preventing eIF2alpha phosphorylation by transfection with constitutively active PP1c regulatory subunit, dominant-negative eIF2alpha kinase PERK, or PERK inhibitor P58(IPK) blocks the energy-deprivation-induced BACE1 increase. Furthermore, chronic treatment of aged Tg2576 mice with energy inhibitors increases levels of eIF2alpha-P, BACE1, Abeta, and amyloid plaques. Importantly, eIF2alpha-P and BACE1 are elevated in aggressive plaque-forming 5XFAD transgenic mice, and BACE1, eIF2alpha-P, and amyloid load are correlated in humans with AD. These results strongly suggest that eIF2alpha phosphorylation increases BACE1 levels and causes Abeta overproduction, which could be an early, initiating molecular mechanism in sporadic AD.
    Neuron 01/2009; 60(6):988-1009. DOI:10.1016/j.neuron.2008.10.047 · 15.98 Impact Factor
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    • "The significant decrement in glucose metabolic rates for the Alzheimer subjects compared to age­ matched controls is consistent with our earlier J Cereb Blood Flow Metab, Vol. 7, No.2, 1987 studies (Ferris et aI., 1980; de Leon et aI., 1983) and those of others (Benson et aI., 1983). However, the similar diminution in frontal, temporal, and parietal activity found in the present study is in disagree­ ment with the more marked decreases found in the parietotemporal area relative to frontal lobe sam­ ples reported by other investigators (Chase et aI., 1983; Friedland et aI., 1983). "
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    ABSTRACT: Elderly controls and probable Alzheimer's disease patients underwent serial positron emission tomography (PET) studies during a baseline condition and while performing a verbal memory task. For the temporal lobes, all 7 Alzheimer patients demonstrated a relative shift in glucose metabolic rates to the right hemisphere during the memory condition relative to baseline, and 5 of 7 controls showed a shift to the left hemisphere. Baseline absolute regional metabolic rates replicate previous findings and were somewhat less useful than the memory challenge in differentiating patients from controls. These results indicate that a temporal lobe abnormality in Alzheimer's disease is related to memory performance.
    Journal of Cerebral Blood Flow & Metabolism 05/1987; 7(2):248-51. DOI:10.1038/jcbfm.1987.50 · 5.34 Impact Factor
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