Aβ deposits in older non-demented individuals with cognitive decline are indicative of preclinical Alzheimer's disease

Villemagne, Victor L.; Pike, Kerryn E.; Darby, David; Maruff, Paul; Savage, Greg; Ng, Serena; Ackermann, Uwe; Cowie, Tiffany; Currie, Jay D.; Chan, Shan-Ho; Jones, Gareth; Tochon-Danguy, Henri; O’Keefe, Graeme; Masters, Colin L.; Rowe, Christopher C.

doi:10.1016/j.neuropsychologia.2008.02.008

Cited by 268 publications

(200 citation statements)

References 85 publications

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“…Studies incorporating postmortem confirmation of AD can avoid this problem, but for most studies this is not possible, hence this diagnostic inaccuracy should be considered when interpreting results. A significant number of healthy controls (30%) may be high-risk clinically silent individuals, further confounding interpretation [43][44].…”

Section: Another Promising Approach Is Pet Imaging Employing Ligandsmentioning

confidence: 99%

Ocular Biomarkers for Early Detection of Alzheimer's Disease

Frost

Martins

Kanagasingam

2010

JAD

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Alzheimer's disease (AD) is the most common form of dementia and is characterized clinically by a progressive decline in memory, learning and executive function and neuropathologically by the presence of cerebral amyloid deposits. Despite a century of research, there is still no cure or conclusive pre-mortem diagnosis for the disease. A number of symptom-modifying drugs for AD have been developed, but their efficacy is minimal and short-lived. AD cognitive symptoms arise only after significant, irreversible neural deterioration has occurred, hence there is an urgent need to detect AD early, before the onset of cognitive symptoms. An accurate, early diagnostic test for AD would enable current and future treatments to be more effective, as well as contribute to the development of new treatments.While most AD related pathology occurs in the brain, the disease has also been reported to affect the eye, which is more accessible for imaging than the brain. AD-related proteins exist in the normal human eye and may produce ocular pathology in AD. There is some homology between the retinal and cerebral vasculatures and the retina also contains nerve cells and fibers that form a sensory extension of the brain. The eye is the only place in the body where vasculature or neural tissue is available for non-invasive optical imaging. This article presents a review of current literature on ocular morphology in AD and discusses the potential for an ocular based screening test for AD.

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Section: Another Promising Approach Is Pet Imaging Employing Ligandsmentioning

confidence: 99%

Ocular Biomarkers for Early Detection of Alzheimer's Disease

Frost

Martins

Kanagasingam

2010

JAD

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“…Nonetheless, average 11 C-PiB PET retention in DLB brains was lower, reflecting a larger spectrum of Ab deposition (1). Interestingly, about 20%-25% of the cognitively normal elderly subjects who were evaluated showed cortical binding predominantly in the prefrontal and posterior cingulate/ precuneus regions, though to a lesser degree than did AD patients (1,10,11).…”

mentioning

confidence: 99%

“…First, the contribution of Lewy bodies (LBs) to 11 C-PiB PET retention in DLB patients has been studied. LBs are primarily composed of aggregated a-synuclein and, like Ab, are thioflavin T-positive.…”

mentioning

confidence: 99%

Characterization of PiB Binding to White Matter in Alzheimer Disease and Other Dementias

Fodero‐Tavoletti¹,

Rowe²,

McLean³

et al. 2009

J Nucl Med

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11 C-Pittsburgh Compound B ( 11 C-PiB) PET has demonstrated significantly higher PiB retention in the gray matter of Alzheimer disease (AD) patients than in healthy controls (HCs). PiB is similarly retained within the white matter of HC and AD brains. Although the specificity of PiB for Ab plaques in gray matter has been well described, the nature of PiB binding to white matter remains unclear. In this study, we characterized the binding of PiB to human white matter homogenates. Methods: In vitro binding studies were conducted using 3 H-PiB (0.1-500 nM) and white matter brain homogenates (100 mg) from 3 AD patients and 3 HCs. Nonspecific binding was determined using PiB (1 mM). White matter from the same patients was also analyzed by immunofluorescence/immunohistochemistry (IF/IHC) microscopy and Western blotting for Ab expression. White matter kinetics were also characterized in vivo through 11 C-PiB PET studies in 27 HCs and 34 patients with dementia. IF/IHC experiments were conducted on 1 postmortem patient with dementia, to compare with the 11 C-PiB distribution volume ratio data acquired 23 mo earlier. Results: In vitro saturation studies indicated that 3 HPiB binds nonspecifically to white matter brain homogenates. PiB fluorescence staining of AD and HC brain sections was consistent with absence of Ab in IHC staining. Higher gray matterto-white matter ratios were observed in IHC images than in 11 C-PiB PET images. Conclusion: These studies suggest that PiB binding to white matter is mainly nonsaturable and nonspecific and that PiB retention in the 11 C-PiB PET studies is largely attributable to slower PiB white matter kinetics.

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“…Interestingly enough, high 11 C-PIB retention has been observed in healthy elderly control subjects (106,142,143). Some 11 C-PIB-positive elderly healthy controls have demonstrated impairment on cognitive tests (137), whereas other 11 C-PIB-positive healthy controls have shown normal cognition (144).…”

Section: Amyloid Imagingmentioning

confidence: 99%

Target-Specific PET Probes for Neurodegenerative Disorders Related to Dementia

Kadir¹,

Nordberg²

2010

J Nucl Med

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Dementia is a highly prevalent problem causing considerable disability and mortality and exacting great costs to individuals, their families, and society. The 4 most common neurodegenerative disorders that cause dementia-Alzheimer disease, frontotemporal dementia, dementia with Lewy bodies, and dementia in Parkinson disease-have different underlying etiologies and pathogenetic mechanisms. There is a great need for early diagnostic markers; functional brain imaging may therefore assist in the detection and differential diagnosis of dementia due to neurodegenerative diseases. Functional imaging such as PET allows in vivo imaging of functional brain activity indicating cerebral blood flow and cerebral glucose metabolism, and PET allows imaging of neurotransmitter activity, including that of the cholinergic, dopaminergic, and serotonergic systems. New PET neuroimaging tracers are being developed for detecting pathologic parameters such as amyloid plaque and microglial activity. The development of molecular imaging is important for early diagnosis of dementia, selection of patients for therapies, and evaluation of therapies.

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Aβ deposits in older non-demented individuals with cognitive decline are indicative of preclinical Alzheimer's disease

Cited by 268 publications

References 85 publications

Ocular Biomarkers for Early Detection of Alzheimer's Disease

Ocular Biomarkers for Early Detection of Alzheimer's Disease

Characterization of PiB Binding to White Matter in Alzheimer Disease and Other Dementias

Target-Specific PET Probes for Neurodegenerative Disorders Related to Dementia

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