18F-FDG PET hypometabolism patterns reflect clinical heterogeneity in sporadic forms of early-onset Alzheimer's disease

Vanhoutte, Matthieu; Semah, Franck; Sillaire, Adeline Rollin; Jaillard, Assia; Petyt, G.; Kuchcinski, Grégory; Maureille, Aurélien; Delbeuck, Xavier; Fahmi, Rachid; Pasquier, Florence; Lopes, Renaud

doi:10.1016/j.neurobiolaging.2017.08.009

Cited by 29 publications

(34 citation statements)

References 66 publications

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“…While fludeoxyglucose positron emission tomography ( 18 F-FDG-PET) helps to detect the cerebral metabolic rate of glucose metabolism (MRglc) in AD [ 41 ], voxel-based morphometry (VBM) of T1-weighted magnetic resonance imaging (MRI) could reveal brain atrophy [ 42 ]. Recent 18 F-FDG-PET studies confirm hypometabolism in early sporadic AD [ 43 , 44 ]. Moreover, region-specific severe hypometabolism in AD brain regions shows age invariance with greatly reduced frontal cortex glucose metabolism [ 45 , 46 ].…”

Section: Introductionmentioning

confidence: 99%

Possible Clues for Brain Energy Translation via Endolysosomal Trafficking of APP‐CTFs in Alzheimer’s Disease

Sivanesan

Mundugaru

Rajadas

2018

Oxidative Medicine and Cellular Longevity

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Vascular dysfunctions, hypometabolism, and insulin resistance are high and early risk factors for Alzheimer's disease (AD), a leading neurological disease associated with memory decline and cognitive dysfunctions. Early defects in glucose transporters and glycolysis occur during the course of AD progression. Hypometabolism begins well before the onset of early AD symptoms; this timing implicates the vulnerability of hypometabolic brain regions to beta-secretase 1 (BACE-1) upregulation, oxidative stress, inflammation, synaptic failure, and cell death. Despite the fact that ketone bodies, astrocyte-neuron lactate shuttle, pentose phosphate pathway (PPP), and glycogenolysis compensate to provide energy to the starving AD brain, a considerable energy crisis still persists and increases during disease progression. Studies that track brain energy metabolism in humans, animal models of AD, and in vitro studies reveal striking upregulation of beta-amyloid precursor protein (β-APP) and carboxy-terminal fragments (CTFs). Currently, the precise role of CTFs is unclear, but evidence supports increased endosomal-lysosomal trafficking of β-APP and CTFs through autophagy through a vague mechanism. While intracellular accumulation of Aβ is attributed as both the cause and consequence of a defective endolysosomal-autophagic system, much remains to be explored about the other β-APP cleavage products. Many recent works report altered amino acid catabolism and expression of several urea cycle enzymes in AD brains, but the precise cause for this dysregulation is not fully explained. In this paper, we try to connect the role of CTFs in the energy translation process in AD brain based on recent findings.

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Section: Introductionmentioning

confidence: 99%

Possible Clues for Brain Energy Translation via Endolysosomal Trafficking of APP‐CTFs in Alzheimer’s Disease

Sivanesan

Mundugaru

Rajadas

2018

Oxidative Medicine and Cellular Longevity

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“…Different networks are specifically involved depending on the neuropsychological presentation. Although the Default Mode Network (DMN) is involved in all AD subtypes, focal patterns of hypometabolism characterize each variant: the left temporoparietal cortex in the logopenic variant, the ventral DMN in the early‐onset or the bilateral prefrontal cortex in the executive/frontal variants (Lehmann et al, ; Vanhoutte et al, ).…”

Section: Discussionmentioning

confidence: 99%

Characterization of a temporoparietal junction subtype of Alzheimer's disease

Meyer

Wehenkel

Phillips

et al. 2019

Human Brain Mapping

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Alzheimer's disease (AD) subtypes have been described according to genetics, neuropsychology, neuropathology, and neuroimaging. Thirty-one patients with clinically probable AD were selected based on perisylvian metabolic decrease on FDG-PET.They were compared to 25 patients with a typical pattern of decreased posterior metabolism. Tree-based machine learning was used on those 56 images to create a classifier that was subsequently applied to 207 Alzheimer's Disease Neuroimaging Initiative (ADNI) patients with AD. Machine learning was also used to discriminate between the two ADNI groups based on neuropsychological scores. Compared to AD patients with a typical precuneus metabolic decrease, the new subtype showed stronger hypometabolism in the temporoparietal junction. The classifier was able to distinguish the two groups in the ADNI population. Both groups could only be distinguished cognitively by Trail Making Test-A scores. This study further confirms that there is more than a typical metabolic pattern in probable AD with amnestic presentation. K E Y W O R D SAlzheimer, FDG-PET, machine learning, neuroimaging, subtypes

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“…A korai kezdetű AD (earlyonset Alzheimer's disease, EOAD) esetében a bal praecuneus területén mérhető kifejezett glükózanyagcserecsökkenés. Ez az elváltozás nagyobb mértékű, kiterjedtebb és gyorsabban progrediáló folyamattal társul, mint a jobb cingularis kérget érintő késői típusú AD (late-onset Alzheimer's disease, LOAD) [14,15]. Az EOADban érintett betegeknél tapasztalták, hogy a kifejezett metabolikus változást mutató területekben hiányzik a specifikus β-amiloid-patológia.…”

Section: A Glükózanyagcsere Feltérképezéseunclassified

“…Az EOADban érintett betegeknél tapasztalták, hogy a kifejezett metabolikus változást mutató területekben hiányzik a specifikus β-amiloid-patológia. Ez arra utal, hogy ezen klinikai megjelenés hátterében nagyobbrészt anyagcsereváltozások állnak, és nem a kóros fehérjelerakódás [15].…”

Section: A Glükózanyagcsere Feltérképezéseunclassified

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Az Alzheimer-kór molekuláris képi megjelenítése

Albert

Borbély

2019

Orvosi Hetilap

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The ever-growing average age of the society significantly increases the occurrence of Alzheimer’s disease. The increased prevalence represents considerable social and economic burden, which urges the development of diagnostic and therapeutic methods in the field. The most common cause of dementia is Alzheimer’s disease, the typical histopathological abnormality of which are well known. The detection of functional changes results in the early diagnosis of the disease, which precedes the morphological changes by years. Positron-emission tomography plays an important role in the demonstration of metabolic changes. The glucose metabolic pattern differs significantly in each clinical form of dementia. The most important β-amyloid-binding radiopharmaceuticals that should be highlighted are [11C]Pittsburgh compound B that is widely used in the research and [18F]florbetapir that is commonly approved in diagnostics. Tracers visualising neurofibrillary tangles consisting of tau protein appeared most recently. The development continues; newer and newer radiopharmaceuticals appear. These tracers play an important role in both the research and the diagnostics. Orv Hetil. 2019; 160(33): 1289–1295.

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18F-FDG PET hypometabolism patterns reflect clinical heterogeneity in sporadic forms of early-onset Alzheimer's disease

Cited by 29 publications

References 66 publications

Possible Clues for Brain Energy Translation via Endolysosomal Trafficking of APP‐CTFs in Alzheimer’s Disease

Possible Clues for Brain Energy Translation via Endolysosomal Trafficking of APP‐CTFs in Alzheimer’s Disease

Characterization of a temporoparietal junction subtype of Alzheimer's disease

Az Alzheimer-kór molekuláris képi megjelenítése

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