Aβ Imaging in Aging, Alzheimer’s Disease, and Other Neurodegenerative Conditions

Villemagne, Victor L.; Doré, Vincent; Burnham, Samantha; Rowe, Christopher C.

doi:10.1007/978-3-030-53168-3_10

Cited by 6 publications

(8 citation statements)

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“…This imaging sequence allows to detect neuronal activity during resting state or task performance, and is the primary technique to analyze cognitive performance ( Jezzard and Ramsey, 2003 ). Lastly, positron emission tomography (PET) is a functional imaging technique that visualizes and measures cerebral blood flow, metabolism, regional chemical composition, absorption, and the presence of targeted disease biomarkers ( Villemagne et al, 2021 ). Following the injection of a protein-specific tracer, PET is used to quantify the standardized uptake value which measures the concentration of the tracer that has adhered to its target ( Phelps and Mazziotta, 1985 ).…”

Section: Common Neuroimaging Tools and Imaging Sequences Used To Quantify Aging-related Brain Changesmentioning

confidence: 99%

Brain aging mechanisms with mechanical manifestations

Blinkouskaya

Caçoilo

Gollamudi

et al. 2021

Mechanisms of Ageing and Development

117

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Brain aging is a complex process that affects everything from the subcellular to the organ level, begins early in life, and accelerates with age. Morphologically, brain aging is primarily characterized by brain volume loss, cortical thinning, white matter degradation, loss of gyrification, and ventricular enlargement. Pathophysiologically, brain aging is associated with neuron cell shrinking, dendritic degeneration, demyelination, small vessel disease, metabolic slowing, microglial activation, and the formation of white matter lesions. In recent years, the mechanics community has demonstrated increasing interest in modeling the brain’s (bio)mechanical behavior and uses constitutive modeling to predict shape changes of anatomically accurate finite element brain models in health and disease. Here, we pursue two objectives. First, we review existing imaging-based data on white and gray matter atrophy rates and organ-level aging patterns. This data is required to calibrate and validate constitutive brain models. Second, we review the most critical cell- and tissue-level aging mechanisms that drive white and gray matter changes. We focuse on aging mechanisms that ultimately manifest as organ-level shape changes based on the idea that the integration of imaging and mechanical modeling may help identify the tipping point when normal aging ends and pathological neurodegeneration begins.

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Section: Common Neuroimaging Tools and Imaging Sequences Used To Quantify Aging-related Brain Changesmentioning

confidence: 99%

Brain aging mechanisms with mechanical manifestations

Blinkouskaya

Caçoilo

Gollamudi

et al. 2021

Mechanisms of Ageing and Development

117

View full text Add to dashboard Cite

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“…We identified imaging tracers a priori for inclusion in this review based on established evidence for their efficacy. The recent reviews by Okamura and colleagues 39 and Villemagne and Okamura 24 served as a scaffold for selection of tau-selective radioligands for this review, and identification of 18F-FDDNP as a dual tracer of tau and b-amyloid. Radioisotopes identified by these reviews as being tau selective are as follows: 18F-THK-5105, 18F-THK-5117, 18F-THK-5351, 18F-AV-1451 (18F-T807), 11C-PBB3, and 18F-RO6958948.…”

Section: Eligibility Criteriamentioning

confidence: 99%

“…Researchers have grappled with pathological (and in some instances phenotypical) similarities between CTE and other tauopathies such as Alzheimer's disease (AD), progressive supranuclear palsy (PSP), Pick's disease, and corticobasal degeneration, all of which involve varying degrees of tauopathy or amyloidopathy. Disease-specific isoform compositions of tau have been identified in these neurodegenerative conditions that may allow for targeted radioimaging (see Villemagne and Okamura 24 for a recent review of tau imaging in neurodegenerative disease). Overall, the intraneuronal composition of neurofibrillary tangles found in CTE is not distinct to the form seen in Alzheimer's disease.…”

Section: Introductionmentioning

confidence: 99%

A Systematic Review of Positron Emission Tomography of Tau, Amyloid Beta, and Neuroinflammation in Chronic Traumatic Encephalopathy: The Evidence To Date

Lee

Leavitt

Bernick

et al. 2018

Journal of Neurotrauma

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Chronic traumatic encephalopathy (CTE) is associated with pathological changes, yet detecting these changes during life has proven elusive. Positron emission tomography (PET) offers the potential for identifying such pathology. Few studies have been completed to date and their approaches and results have been diverse. It was the objective of this review to systematically examine relevant research using ligands for PET that bind to identified pathology in CTE. We focused on identification of patterns of binding and addressing gaps in knowledge of PET imaging for CTE. A comprehensive literature search was conducted. Data used were published on or before May 22, 2017. As the extant literature is limited, any peer-reviewed article assessing military, contact sports athletes, or professional fighters was considered for inclusion. The main outcomes were regional binding to brain regions identified through control comparisons or through clinical metrics (e.g., standardized uptake volume ratios). A total of 1207 papers were identified for review, of which six met inclusion criteria. Meta-analyses were planned but were deemed inappropriate given the small number of studies identified. Methodological concerns in these initial papers included small sample sizes, lack of a control comparison, use of nonstandard statistical procedures to quantify data, and interpretation of potentially off-target binding areas. Across studies, the hippocampi, amygdalae, and midbrain had reasonably consistent increased uptake. Evidence for increased uptake in cortical regions was less consistent. The evidence suggests that the field of PET imaging in those at risk for CTE remains nascent. As the field evolves to include more stringent studies, ligands for PET may prove an important tool in identifying CTE in vivo.

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“…Amyloid-β (Aβ) and tau are the two main neuropathological hallmarks of AD [4][5][6]. The advent of minimally invasive and in-vivo imaging of Aβ and tau in the human brain as well as high resolution structural imaging enables investigation of the link between well-documented AD neuropathology and neurodegeneration [7][8][9]. There are inconsistent reports about the relationship between neurodegeneration and these two pathologies, especially Aβ deposition.…”

Section: Introductionmentioning

confidence: 99%

Distinct and joint effects of low and high levels of Aβ and tau deposition on cortical thickness

Hojjati

Butler

Chiang

et al. 2022

Preprint

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Alzheimer's disease (AD) is defined by the presence of Amyloid-β (Aβ), tau, and neurodegeneration (ATN framework) in the human cerebral cortex. Prior studies have suggested that Aβ deposition can be associated with both cortical thinning and thickening. These contradictory results may be due to small sample sizes, the presence versus absence of tau, and limited detectability in the earliest phase of protein deposition, which may begin in young adulthood and cannot be captured in studies enrolling only older subjects. In this study, we aimed to find the distinct and joint effects of Aβ and tau on neurodegeneration during the progression from normal to abnormal stages of pathologies that remain incompletely understood. We used 18F-MK6240 and 18F-Florbetaben/18F-Florbetapir positron emission tomography (PET) and magnetic resonance imaging (MRI) to quantify tau, Aβ, and cortical thickness in 529 participants ranging in age from 20 to 90. We applied a novel partial volume correction technique based on the absence of proteinopathy in young controls to optimize spatial resolution. Aβ/tau abnormality was defined at 95th percentile of the normal distribution of global Ab/tau observed in young participants. We performed multiple regression analyses to assess the distinct and joint effects of Aβ and tau on cortical thickness. Using 529 participants (83 young, 394 healthy older, 52 MCI) we showed that normal levels of Aβ deposition were significantly associated with increased cortical thickness regardless of the amount of tau (e.g., left entorhinal cortex with t>3.241). The relationship between tau deposition and neurodegeneration was more complex: abnormal levels of tau were associated with cortical thinning in several regions of the brain (e.g., left entorhinal with t<-2.80 and left insula with t<-3.202), as expected based on prior neuroimaging and neuropathological studies. Surprisingly, however, normal levels of tau were found to be associated with cortical thickening. Moreover, at abnormal levels of Aβ and tau, the resonance between them, defined as their correlation throughout the cortex, was associated strongly with cortical thinning when controlling for their additive effect. We confirm prior findings of an association between Aβ deposition and cortical thickening and suggest this may also be the case in the earliest stages of deposition in normal aging. We discuss potential pathophysiologic processes underlying this effect such as inflammation and hyperactivation (excitotoxicity). We also illustrate that resonance between high levels of Aβ and tau uptake is strongly associated with cortical thinning, emphasizing the effects of Aβ/tau synergy in AD pathogenesis.

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Aβ Imaging in Aging, Alzheimer’s Disease, and Other Neurodegenerative Conditions

Cited by 6 publications

References 453 publications

Brain aging mechanisms with mechanical manifestations

Brain aging mechanisms with mechanical manifestations

A Systematic Review of Positron Emission Tomography of Tau, Amyloid Beta, and Neuroinflammation in Chronic Traumatic Encephalopathy: The Evidence To Date

Distinct and joint effects of low and high levels of Aβ and tau deposition on cortical thickness

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