Association between GAB2 haplotype and higher glucose metabolism in Alzheimer's disease-affected brain regions in cognitively normal APOEε4 carriers

Background: The study aimed to evaluate the appropriate uptake-timing in cognitively normal individuals, mild cognitive impairment (MCI), and Alzheimer’s disease (AD) patients, using 18F-PI 2620 dynamic PET acquisition. Methods: Thirty-four MCI patients, 6 AD patients, and 24 cognitively normal individuals were enrolled in this study. A dynamic 18F-PI 2620 PET study was conducted at 30-75 minutes post-injection in these groups. Co-registration was applied between the dynamic acquisition PET and T1-weighted MRI to delineate various cortical regions. The standardized uptake value ratio (SUVR) was used for quantitative analysis. P-mod software with the Automated Anatomical Labeling (AAL)-merged atlas was employed to generate automatic volumes of interest for 11 brain regions. Results: The curves in most brain regions presented an average SUVR stability at 30-40 minutes post-injection in each group. The appropriate uptake-timing interval of 18F-PI 2620 was 30-75 minutes post injection for AD group and 30-40 minutes post injection for both cognitively normal individuals and MCI groups. Conclusion: Short uptake time around 30-40 minutes post-injection would be more comfortable and convenient for all patients, especially in those with dementia who were unable to stay motionless for long periods of scanning time in the scanner.

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P1-231: Correlation of amyloid deposition with local and distal glucose metabolism in cognitively normal elderly, MCI and Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2008.05.820 ◽

2008 ◽

Vol 4 ◽

pp. T279-T280 ◽

Cited By ~ 2

Author(s):

Ann D. Cohen ◽

Scott Ziolko ◽

Howard Aizenstein ◽

Robert D. Nebes ◽

Judith A. Saxton ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Glucose Metabolism ◽

Amyloid Deposition ◽

Cognitively Normal

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Comparison of [11C]UCB-J and [18F]FDG PET in Alzheimer’s disease: A tracer kinetic modeling study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x211004312 ◽

2021 ◽

pp. 0271678X2110043

Author(s):

Ming-Kai Chen ◽

Adam P Mecca ◽

Mika Naganawa ◽

Jean-Dominique Gallezot ◽

Takuya Toyonaga ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Medial Temporal Lobe ◽

Brain Regions ◽

Volume Of Distribution ◽

Synaptic Density ◽

Cognitively Normal ◽

Tracer Kinetic ◽

Suitable Marker

[11C]UCB-J PET for synaptic vesicle glycoprotein 2 A (SV2A) has been proposed as a suitable marker for synaptic density in Alzheimer’s disease (AD). We compared [11C]UCB-J binding for synaptic density and [18F]FDG uptake for metabolism (correlated with neuronal activity) in 14 AD and 11 cognitively normal (CN) participants. We assessed both absolute and relative outcome measures in brain regions of interest, i.e., K1 or R1 for [11C]UCB-J perfusion, VT (volume of distribution) or DVR to cerebellum for [11C]UCB-J binding to SV2A; and Ki or Ki R to cerebellum for [18F]FDG metabolism. [11C]UCB-J binding and [18F]FDG metabolism showed a similar magnitude of reduction in the medial temporal lobe of AD –compared to CN participants. However, the magnitude of reduction of [11C]UCB-J binding in neocortical regions was less than that observed with [18F]FDG metabolism. Inter-tracer correlations were also higher in the medial temporal regions between synaptic density and metabolism, with lower correlations in neocortical regions. [11C]UCB-J perfusion showed a similar pattern to [18F]FDG metabolism, with high inter-tracer regional correlations. In summary, we conducted the first in vivo PET imaging of synaptic density and metabolism in the same AD participants and reported a concordant reduction in medial temporal regions but a discordant reduction in neocortical regions.

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Tau pathology in cognitively normal older adults

10.1101/611186 ◽

2019 ◽

Author(s):

Jacob Ziontz ◽

Murat Bilgel ◽

Andrea T. Shafer ◽

Abhay Moghekar ◽

Wendy Elkins ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Memory Performance ◽

Brain Regions ◽

Tau Pathology ◽

Cognitively Normal ◽

Rates Of Change ◽

Baltimore Longitudinal Study ◽

Brain Changes ◽

Male Sex

AbstractINTRODUCTIONTau pathology, a hallmark of Alzheimer’s disease, is observed in the brains of virtually all individuals over 70.METHODSUsing 18F-AV-1451 (18F-flortaucipir) PET, we evaluated tau pathology in 54 cognitively normal participants (mean age 77.5, SD 8.9) from the Baltimore Longitudinal Study of Aging. We assessed associations between PET signal and age, sex, race, and amyloid positivity. We investigated relationships between regional signal and retrospective rates of change in regional volumes and cognitive function adjusting for age, sex, and amyloid status.RESULTSGreater age, male sex, black race, and amyloid positivity were associated with higher 18F-AV-1451 retention in distinct brain regions. Retention in the entorhinal cortex was associated with lower entorhinal volume (β = −1.124, SE = 0.485, p = 0.025) and a steeper decline in memory performance (β = −0.086, SE = 0.039, p = 0.029).DISCUSSIONAssessment of medial temporal tau pathology will provide insights into early structural brain changes associated with later cognitive impairment and Alzheimer’s disease.

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Simultaneous PET/fMRI Detects Distinctive Alterations in Functional Connectivity and Glucose Metabolism of Precuneus Subregions in Alzheimer’s Disease

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.737002 ◽

2021 ◽

Vol 13 ◽

Author(s):

Miao Zhang ◽

Wanqing Sun ◽

Ziyun Guan ◽

Jialin Hu ◽

Binyin Li ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Functional Connectivity ◽

Glucose Metabolism ◽

Clustering Algorithm ◽

Brain Network ◽

Resting State Functional Connectivity ◽

Metabolic Pattern ◽

Cognitively Normal ◽

Functional Connectivity Strength

As a central hub in the interconnected brain network, the precuneus has been reported showing disrupted functional connectivity and hypometabolism in Alzheimer’s disease (AD). However, as a highly heterogeneous cortical structure, little is known whether individual subregion of the precuneus is uniformly or differentially involved in the progression of AD. To this end, using a hybrid PET/fMRI technique, we compared resting-state functional connectivity strength (FCS) and glucose metabolism in dorsal anterior (DA_pcu), dorsal posterior (DP_pcu) and ventral (V_pcu) subregions of the precuneus among 20 AD patients, 23 mild cognitive impairment (MCI) patients, and 27 matched cognitively normal (CN) subjects. The sub-parcellation of precuneus was performed using a K-means clustering algorithm based on its intra-regional functional connectivity. For the whole precuneus, decreased FCS (p = 0.047) and glucose hypometabolism (p = 0.006) were observed in AD patients compared to CN subjects. For the subregions of the precuneus, decreased FCS was found in DP_pcu of AD patients compared to MCI patients (p = 0.011) and in V_pcu for both MCI (p = 0.006) and AD (p = 0.008) patients compared to CN subjects. Reduced glucose metabolism was found in DP_pcu of AD patients compared to CN subjects (p = 0.038) and in V_pcu of AD patients compared to both MCI patients (p = 0.045) and CN subjects (p < 0.001). For both FCS and glucose metabolism, DA_pcu remained relatively unaffected by AD. Moreover, only in V_pcu, disruptions in FCS (r = 0.498, p = 0.042) and hypometabolism (r = 0.566, p = 0.018) were significantly correlated with the cognitive decline of AD patients. Our results demonstrated a distinctively disrupted functional and metabolic pattern from ventral to dorsal precuneus affected by AD, with V_pcu and DA_pcu being the most vulnerable and conservative subregion, respectively. Findings of this study extend our knowledge on the differential roles of precuneus subregions in AD.

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Increased phosphoglycerate kinase in the brains of patients with Down's syndrome but not with Alzheimer's disease

Clinical Science ◽

10.1042/cs0960279 ◽

1999 ◽

Vol 96 (3) ◽

pp. 279-285

Author(s):

Olga LABUDOVA ◽

Erwin KITZMUELLER ◽

Hermann RINK ◽

Nigel CAIRNS ◽

Gert LUBEC

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Glucose Metabolism ◽

Down's Syndrome ◽

Phosphoglycerate Kinase ◽

Down’S Syndrome ◽

Brain Regions ◽

Published Data ◽

Transcriptional Level ◽

Impaired Glucose Metabolism

Impaired glucose metabolism in Down's syndrome (DS) has been well-documented in vivo, although information on the underlying biochemical defect is limited and no biochemical studies on glucose handling enzymes have been carried out in the brain. Through gene hunting in fetal DS brain we found an overexpressed sequence homologous to the phosphoglycerate kinase (PGK) gene. This finding was studied further by investigating the activity levels of this key enzyme of carbohydrate metabolism in the brains of patients with DS. PGK activity was determined in five brain regions of nine patients with DS, nine patients with Alzheimer's disease and 14 controls. PGK activity was significantly elevated in the frontal, occipital and temporal lobe and in the cerebellum of patients with DS. PGK activity in corresponding brain regions of patients with Alzheimer's disease was comparable with controls. We conclude that our findings complement previously published data on impaired brain glucose metabolism in DS evaluated by positron emission tomography in clinical studies. Furthermore, we show that in DS, impaired glucose metabolism, represented by increased PGK activity, is a specific finding rather than a secondary phenomenon simply due to neurodegeneration or atrophy. These observations are also supported by data from subtractive hybridization, showing overexpressed PGK in DS brains at the transcriptional level early in life.

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Relationships Between Tau and Glucose Metabolism Reflect Alzheimer’s Disease Pathology in Cognitively Normal Older Adults

Cerebral Cortex ◽

10.1093/cercor/bhy078 ◽

2018 ◽

Vol 29 (5) ◽

pp. 1997-2009 ◽

Cited By ~ 19

Author(s):

Jenna N Adams ◽

Samuel N Lockhart ◽

Lexin Li ◽

William J Jagust

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Glucose Metabolism ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Amyloid Β ◽

Normal Aging ◽

Cognitively Normal ◽

Canonical Correlations

Abstract Tau is associated with hypometabolism in patients with Alzheimer’s disease. In normal aging, the association between tau and glucose metabolism is not fully characterized. We used [18F] AV-1451, [18F] Fluorodeoxyglucose, and [11C] Pittsburgh Compound-B (PiB) PET to measure associations between tau and glucose metabolism in cognitively normal older adults (N = 49). Participants were divided into amyloid-negative (PiB–, n = 28) and amyloid-positive (PiB+, n = 21) groups to determine effects of amyloid-β. We assessed both local and across-brain regional tau–glucose metabolism associations separately in PiB–/PiB+ groups using correlation matrices and sparse canonical correlations. Relationships between tau and glucose metabolism differed by amyloid status, and were primarily spatially distinct. In PiB– subjects, tau was associated with broad regions of increased glucose metabolism. In PiB+ subjects, medial temporal lobe tau was associated with widespread hypometabolism, while tau outside of the medial temporal lobe was associated with decreased and increased glucose metabolism. We further found that regions with earlier tau spread were associated with stronger negative correlations with glucose metabolism. Our findings indicate that in normal aging, low levels of tau are associated with a phase of increased metabolism, while high levels of tau in the presence of amyloid-β are associated with hypometabolism at downstream sites.

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Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x19879226 ◽

2019 ◽

Vol 40 (12) ◽

pp. 2464-2474 ◽

Cited By ~ 5

Author(s):

Tessa Timmers ◽

Rik Ossenkoppele ◽

Denise Visser ◽

Hayel Tuncel ◽

Emma E Wolters ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Quantitative Methods ◽

Standardized Uptake Value ◽

Brain Regions ◽

Reference Region ◽

Reference Tissue ◽

Cognitively Normal ◽

Quantitative Models ◽

Good For

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [18F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [18F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr80–100 and SUVr110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.

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