Dominantly inherited Alzheimer's disease: cerebral glucose metabolism.

Polinsky, R. J.; Noble, H. M.; Chiro, Giovanni Di; Nee, Linda E.; Feldman, Robert G.; Brown, Rg

doi:10.1136/jnnp.50.6.752

Cited by 51 publications

(15 citation statements)

References 27 publications

(9 reference statements)

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“…In agreement with CBF findings, positron emission tomography studies have revealed that reduced regional metabolic rates of glucose in the mesial temporal lobe structures is present in early AD, and correlates with the severity of dementia [84,[87][88][89]. In advanced AD cases, metabolic disturbances also affect the prefrontal and parietal association areas [93].…”

Section: Differential Diagnosis Of Ad and Vad: The Contribution Of Nementioning

confidence: 50%

Reevaluating the Role of Vascular Changes in the Differential Diagnosis of Alzheimer’s Disease and Vascular Dementia

1998

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Alzheimer’s disease (AD) and vascular dementia (VaD) are the two most common causes of dementia, and much effort has been devoted to their differential diagnosis. However, current epidemiological, clinical and neuropathological evidence points to a substantial overlap between AD and VaD and suggests that vascular pathology, the traditional cornerstone of the differential diagnosis between the two entities, may not represent as clear a line of demarcation as originally believed. It may be time to reevaluate the dichotomy between AD and VaD.

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Section: Differential Diagnosis Of Ad and Vad: The Contribution Of Nementioning

confidence: 50%

Reevaluating the Role of Vascular Changes in the Differential Diagnosis of Alzheimer’s Disease and Vascular Dementia

1998

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“…ADAD and sAD are both associated with elevated cortical PiB uptake, especially in the in the precuneus/posterior cingulate and prefrontal cortex (54)(55)(56). Reductions in glucose metabolism in the temporal and parietal lobes have also been observed in both diseases (57)(58)(59)(60). Finally, both LOAD and ADAD have been shown to result in cortical (51,(61)(62)(63)(64)(65) and hippocampal (63,(65)(66)(67)(68) atrophy.…”

Section: Discussionmentioning

confidence: 99%

Regional variability of imaging biomarkers in autosomal dominant Alzheimer’s disease

Benzinger¹,

Blazey²,

Jack

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

323

341

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, and structural atrophy (imaged by MRI). Recently we published the initial subset of imaging findings for specific regions in a cohort of individuals with autosomal dominant Alzheimer's disease. We now extend this work to include a larger cohort, wholebrain analyses integrating all three imaging modalities, and longitudinal data to examine regional differences in imaging biomarker dynamics. The anatomical distribution of imaging biomarkers is described in relation to estimated years from symptom onset. Autosomal dominant Alzheimer's disease mutation carrier individuals have elevated PiB levels in nearly every cortical region 15 y before the estimated age of onset. Reduced cortical glucose metabolism and cortical thinning in the medial and lateral parietal lobe appeared 10 and 5 y, respectively, before estimated age of onset. Importantly, however, a divergent pattern was observed subcortically. All subcortical gray-matter regions exhibited elevated PiB uptake, but despite this, only the hippocampus showed reduced glucose metabolism. Similarly, atrophy was not observed in the caudate and pallidum despite marked amyloid accumulation. Finally, before hypometabolism, a hypermetabolic phase was identified for some cortical regions, including the precuneus and posterior cingulate. Additional analyses of individuals in which longitudinal data were available suggested that an accelerated appearance of volumetric declines approximately coincides with the onset of the symptomatic phase of the disease.neuroimaging | aging | dementia | neurodegeneration | DIAN T he pathological mechanisms underlying nondominantly inherited late onset Alzheimer's disease (LOAD) remain an active area of investigation (1). According to the amyloid cascade hypothesis, the precipitating event in LOAD is an alteration of the balance between production and clearance of the metabolites of amyloid precursor protein (APP) (2). Abnormalities in APP metabolism then lead to β-amyloid (Aβ) deposition in the cerebral cortex, the formation of neurofibrillary tangles (NFTs) containing hyperphosphorylated tau protein, neuronal dysfunction, cell loss, and, ultimately, dementia. In vivo biomarkers of LOAD include cerebrospinal fluid (CSF) Aβ 42 , CSF tau, amyloid deposition imaged with Pittsburgh compound B PET (PiB PET) and other amyloid tracers, altered glucose metabolism imaged with fluro-deoxyglucose PET (FDG PET), and structural atrophy assessed by volumetric MRI. A theoretical model of biomarker changes has been proposed by Jack et al. (3) that links these Significance Beta-amyloid plaque accumulation, glucose hypometabolism, and neuronal atrophy are hallmarks of Alzheimer's disease. However, the regional ordering of these biomarkers prior to dementia remains untested. In a cohort with Alzheimer's disease mutations, we performed an integrated whole-brain analysis of three major imaging techniques: amyloid PET, [18 F] fluro-deoxyglucose PET, and structural MRI. We found that most gray-matter structures with amyloid plaques later have hypometabolism follo...

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“…A severely decreased rate of carbohydrate catabolism is now well established either in the DAT brain [22][23][24] or in fibroblasts from Alzheimer patients [25]. In addition, multiple studies have shown drastic reductions in the DAT brain of several enzymes acting in glycolytic glucose breakdown, such as phosphofructokinase and hexokinase: phosphofructokinase was found to be decreased to 10 [26] and 60% [27] of control values, and hexokinase activity was diminished by 34% compared with normal controls [28].…”

Section: Discussionmentioning

confidence: 99%

Abnormal Substrate Levels That Depend upon Mitochondrial Function in Cerebrospinal Fluid from Alzheimer Patients

Redjems-Bennani

Jeandel²,

Lefebvre³

et al. 1998

Gerontology

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Background: Impaired oxidative and energy metabolism are important features in Alzheimer’s disease. These metabolic abnormalities may induce functional disturbances and are associated with significant cognitive impairment. Objective: To determine whether mitochondrial function is altered by Alzheimer’s disease, a quantitative analysis of substrates that enter the tricarboxylic acid cycle was carried out in cerebrospinal fluid (CSF) from Alzheimer patients. Methods: Organic acid levels related to carbohydrate oxidation were measured in CSF from patients affected by dementia of Alzheimer type (n = 17) and from nondemented elderly controls (n = 17) using a gas chromatography/mass spectrometry system. CSF glucose and glutamine concentrations were determined by a quantitative enzymatic method and by ion exchange chromatography, respectively. Results: Compared to age-matched controls, patients had a higher CSF level of lactate (p = 0.002) and a lower mean level of succinate (p = 0.002), fumarate (p = 0.003) and glutamine (p = 0.0005). The CSF glucose level was not modified. Conclusion: Our results suggest an impairment of mitochondrial oxidative metabolism in brain cells of patients with Alzheimer’s disease.

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Dominantly inherited Alzheimer's disease: cerebral glucose metabolism.

Cited by 51 publications

References 27 publications

Reevaluating the Role of Vascular Changes in the Differential Diagnosis of Alzheimer’s Disease and Vascular Dementia

Reevaluating the Role of Vascular Changes in the Differential Diagnosis of Alzheimer’s Disease and Vascular Dementia

Regional variability of imaging biomarkers in autosomal dominant Alzheimer’s disease

Abnormal Substrate Levels That Depend upon Mitochondrial Function in Cerebrospinal Fluid from Alzheimer Patients

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