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[F-18]FDDNP microPET imaging correlates with brain A? burden in a transgenic rat model of Alzheimer disease: effects of aging, in vivo blockade, and anti-A? antibody treatment.

ABSTRACT: In vivo detection of Alzheimer's disease (AD) neuropathology in living patients using positron emission tomography (PET) in conjunction with high affinity molecular imaging probes for ?-amyloid (A?) and tau has the potential to assist with early diagnosis, evaluation of disease progression, and assessment of therapeutic interventions. Animal models of AD are valuable for exploring the in vivo binding of these probes, particularly their selectivity for specific neuropathologies, but prior PET experiments in transgenic mice have yielded conflicting results. In this work, we utilized microPET imaging in a transgenic rat model of brain A? deposition to assess [F-18]FDDNP binding profiles in relation to age-associated accumulation of neuropathology. Cross-sectional and longitudinal imaging demonstrated that [F-18]FDDNP binding in the hippocampus and frontal cortex progressively increases from 9 to 18months of age and parallels age-associated A? accumulation. Specificity of in vivo [F-18]FDDNP binding was assessed by naproxen pretreatment, which reversibly blocked [F-18]FDDNP binding to A? aggregrates. Both [F-18]FDDNP microPET imaging and neuropathological analyses revealed decreased A? burden after intracranial anti-A? antibody administration. The combination of this non-invasive imaging method and robust animal model of brain A? accumulation allows for future longitudinal in vivo assessments of potential therapeutics for AD that target A? production, aggregation, and/or clearance. These results corroborate previous analyses of [F-18]FDDNP PET imaging in clinical populations.

SUBMITTER: Teng E

PROVIDER: S-EPMC3144750 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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[F-18]FDDNP microPET imaging correlates with brain Aβ burden in a transgenic rat model of Alzheimer disease: effects of aging, in vivo blockade, and anti-Aβ antibody treatment.

Teng Edmond E Kepe Vladimir V Frautschy Sally A SA Liu Jie J Satyamurthy Nagichettiar N Yang Fusheng F Chen Ping-Ping PP Cole Graham B GB Jones Mychica R MR Huang Sung-Cheng SC Flood Dorothy G DG Trusko Stephen P SP Small Gary W GW Cole Gregory M GM Barrio Jorge R JR

Neurobiology of disease 20110513 3

In vivo detection of Alzheimer's disease (AD) neuropathology in living patients using positron emission tomography (PET) in conjunction with high affinity molecular imaging probes for β-amyloid (Aβ) and tau has the potential to assist with early diagnosis, evaluation of disease progression, and assessment of therapeutic interventions. Animal models of AD are valuable for exploring the in vivo binding of these probes, particularly their selectivity for specific neuropathologies, but prior PET exp ...[more]

PMID: 21605674

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Project description:Alzheimer's disease (AD) is the most common form of dementia in the elderly, causing neuronal degeneration and cognitive deficits that significantly impair independence and quality of life for those affected and their families. Though AD is a major neurodegenerative disease with vast avenues of investigation, there is no effective treatment to cure AD or slow disease progression. The present work evaluated the therapeutic effect of long-term photobiomodulation (PBM) treatment with continuous-wave low-level laser on AD and its underlying mechanism. Methods: PBM was implemented for 2 min, 3 times per week for 16 months in 2-month-old transgenic AD rats. A battery of behavioral tests was performed to measure the effect of PBM treatment on cognitive dysfunction in AD rats. The effects of PBM therapy on typical AD pathologies, including amyloid plaques, intracellular neurofibrillary tangles, neuronal loss, neuronal injury, neuronal apoptosis, and neurodegeneration, were then assessed. The underlying mechanisms were measured using immunofluorescence staining, western blotting analysis, mass spectrometry, primary cortical and hippocampal cell cultures, and related assay kits. Results: PBM treatment significantly improved the typical AD pathologies of memory loss, amyloid plaques, tau hyperphosphorylation, neuronal degeneration, spine damage, and synaptic loss. PBM treatment had several mechanistic effects which may explain these beneficial effects, including 1) regulation of glial cell polarization and inhibition of neuroinflammation, 2) preservation of mitochondrial dynamics by regulating fission and fusion proteins, and 3) suppression of oxidative damage to DNA, proteins, and lipids. Furthermore, PBM enhanced recruitment of microglia surrounding amyloid plaques by improving the expression of microglial IL-3Rα and astrocytic IL-3, which implies a potential role of PBM in improving Aβ clearance. Finally, our results implicate neuronal hemoglobin in mediating the neuroprotective effect of PBM, as Hbα knockdown abolished the neuroprotective effect of PBM treatment. Conclusion: Collectively, our data supports the potential use of PBM treatment to prevent or slow the progression of AD and provides new insights into the molecular mechanisms of PBM therapy.

Dataset Information

[F-18]FDDNP microPET imaging correlates with brain A? burden in a transgenic rat model of Alzheimer disease: effects of aging, in vivo blockade, and anti-A? antibody treatment.

Publications

[F-18]FDDNP microPET imaging correlates with brain Aβ burden in a transgenic rat model of Alzheimer disease: effects of aging, in vivo blockade, and anti-Aβ antibody treatment.

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