Alzheimer Disease: New Concepts on Its Neurobiology and the Clinical Role Imaging Will Play

Jack, Clifford R.

doi:10.1148/radiol.12110433

Cited by 193 publications

(149 citation statements)

References 276 publications

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“…The 11 C Pittsburgh compound (PiB) has always been the most validated tracer for imaging amyloid pathology. However, there is now a new tracer, 18 F-florebetapir that, thanks to the longer half-life of the radioactive isotope 18 F (110 versus 20 min for the 11 C of 11 C-PiB), has the potential to be used even more extensively both for clinical and research purposes [22].…”

Section: Biomarkersmentioning

confidence: 99%

FDG PET and the genetics of dementia

Nacmias

Berti

Piaceri

et al. 2013

Clin Transl Imaging

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Dementias are the most common neurodegenerative diseases and they are increasingly becoming a major public health problem. The most common form of dementia, affecting over 20 million people worldwide, is Alzheimer's disease (AD). AD is a neurodegenerative disease of the central nervous system mainly found in older adults, with an incidence that increases with age. With the development of newer technologies, including genetic screening technologies and PET/MRI scanning, the role of genetic studies and neuroimaging is being redefined; indeed, these approaches are able to provide support not only in the clinical diagnosis of dementia, but also in its presymptomatic evaluation. Many researchers agree that early identification of AD, before abnormal accumulation of amyloid and tau proteins, could provide an opportunity to hinder the progression of the disease. [18 F]2-fluoro-2-deoxy-D-glucose (FDG) PET studies have shown that decreased glucose metabolism in AD precedes clinical diagnosis and that the degree of clinical disability in AD correlates closely with the magnitude of the reduction in brain glucose metabolism. Data on presymptomatic mutation carriers from families with known early-onset autosomal dominant AD (familial AD) show reductions in the cerebral metabolic rate of glucose (CMRglc), consistent with the expected AD PET pattern, in the absence of severe atrophy on MRI. These results suggest that PET CMRglc measures have the potential to serve as preclinical biomarkers of dementia, useful also for tracking disease progression. This review highlights the role of genetics and FDG PET in understanding the pathogenesis of dementia.

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Section: Biomarkersmentioning

confidence: 99%

FDG PET and the genetics of dementia

Nacmias

Berti

Piaceri

et al. 2013

Clin Transl Imaging

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“…The current estimated prevalence in the United States is 5.3 million individuals, 5.1 million of whom are over 65 years [2]. The global prevalence of the disease is estimated around 24 million in 2001, and predicted to double every 20 years, affecting more than 80 million people by 2040 [3].…”

Section: Epidemiologymentioning

confidence: 99%

“…By 2050, the estimated cost of AD in the United States will exceed $1 trillion per year. The total cost from 2011 through 2050 is estimated at $20 trillion [2]. This health problem is not limited to the United States but estimates of global costs of AD in 2009 were $604 billion per year.…”

Section: Epidemiologymentioning

confidence: 99%

“…NFTs are intracellular aggregates, while Aβ plaques aggregated in the extracellular space. Other pathologic features are represented by the periplaque inflammatory reaction and neurodegeneration (synapse loss, neuron loss, and cerebral atrophy) [2]. The neurofibrillary pathologic process begins in the transentorhinal area and progresses to the hippocampus, to paralimbic and adjacent medial-basal temporal cortex, to neocortical association areas, and then to primary sensorimotor and visual areas [2].…”

Section: Pathophysiology and Clinical Manifestationmentioning

confidence: 99%

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Biomarkers for the early diagnosis of Alzheimer’s disease: The challenge of XXI century

Contino¹,

Cantore²,

Leopoldo³

et al. 2013

AAD

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AD is the most common form of dementia among the aging population. The neuropathological alterations of AD are represented by the neurofibrillary tangles and extracellular amyloid plaques formation. These two hallmarks are routinely used as biomarkers for AD diagnosis and can allow the identification of the pathology in a late phase. The urgent need to develop probes for PET analysis that can be used in an early diagnosis of this disorder opened a new scenario in which new biomarkers involved in the first step of AD can be easily detected. Recently, an increasing number of studies indicated as new biomarkers P-gp, TLR4, MIR and free serum copper that are involved in the onset of AD. It has been extensively reported that a P-gp dysfunction in brain can be considered one of the causes of the AD accumulation in brain parenchyma and that the up-regulation of inflammatory gene expression and inflammatory signaling due to MIR and TLR4 modulated the development and the progression of AD.

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“…[4][5][6] To discover more effective treatments, a reliable diagnostic tool is really needed. 7 Neuroimaging of AD is one of the most active as well as most challenging areas in neuroscience.…”

mentioning

confidence: 99%

Synthesis of a PET tau tracer [11C]PBB3 for imaging of Alzheimer’s disease

Wang

Gao

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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Abstract-The authentic standard PBB3 and its precursor N-desmethyl-PBB3 as well as TBS-protected N-desmethyl-PBB3 precursor for radiolabeling were synthesized from 5-bromo-2-nitropyridine, acrolein diethyl acetal, 6-methoxy-2-methylbenzothiazole, and diethylchlorophosphate with overall chemical yield 1% in six steps, 2% in five steps, and 1% in six steps, respectively. [11 C]PBB3 was prepared from either desmethyl-PBB3 or TBS-protected desmethyl-PBB3 with [11 C]CH 3 OTf through N-[ 11 C]methylation and isolated by HPLC combined with SPE in 20-25% and 15-20% radiochemical yield, respectively, based on [ 11 C]CO 2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity at EOB was 370-1110 GBq/mol with a total synthesis time of ~40-minutes from EOB.

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Alzheimer Disease: New Concepts on Its Neurobiology and the Clinical Role Imaging Will Play

Cited by 193 publications

References 276 publications

FDG PET and the genetics of dementia

FDG PET and the genetics of dementia

Biomarkers for the early diagnosis of Alzheimer’s disease: The challenge of XXI century

Synthesis of a PET tau tracer [11C]PBB3 for imaging of Alzheimer’s disease

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