A FISIOPATOLOGIA DA DOENÇA DE ALZHEIMER ATRAVÉS DO PET

Schilling, Lucas Porcello; Zimmer, Eduardo R.; Shin, Monica; Leuzy, Antoine; Pascoal, Tharick A.; Benedet, Andréa L.; Borelli, Wyllians Vendramini; Palmini, André; Gauthier, Serge; Rosa-Neto, Pedro

doi:10.1590/S1980-5764-2016DN1002003

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Dementia & Neuropsychologia

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Views & Reviews • Dement. neuropsychol. 10 (02) • Apr-Jun 2016 • https://doi.org/10.1590/S1980-5764-2016DN1002003 copiar

A FISIOPATOLOGIA DA DOENÇA DE ALZHEIMER ATRAVÉS DO PET

Autoria SCIMAGO INSTITUTIONS RANKINGS

RESUMO

A doença de Alzheimer tem sido reconceitualizada como um processo patofisiológico dinâmico caracterizado pelos estágios pré-clínico, comprometimento cognitivo leve e demência. A tomografia por emissão de pósitrons associada a vários agentes de imagem molecular revela numerosos aspectos da patofisiologia da demência tais como amiloidose cerebral, acúmulo de tau, mudanças em neurorreceptores, anormalidades de metabolismo e neuroinflamação nestes pacientes. No contexto de um crescimento em direção ao diagnóstico precoce pré-sintomático e intervenções modificadores da doença, a imagem de PET com agentes moleculares fornece meio para quantificar o processo patofisiológico da DA sem precedentes, monitorizar a progressão da doença, bem como quantificar resposta farmacológica. Aqui, nós realçamos as mais importantes contribuições do PET na descrição de anormalidades moleculares cerebrais na DA.

Palavras-chave:
doença de Alzheimer; tomografia por emissão de positron; imagem amilóide; neuroinflamação; neurodegeneração; tau

	[^¹¹11. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011;7(3):263-9.C]PIB	[^¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F]Flutemetamol	[¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F]Florbetapir	[^¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F]Florbetaben	[^¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F]NAV4694
	Research Use	Vizamyl^(r)	Amivid^(r)	Neuraceq^(r)	Phase 3
Alternative name	-	GE-067	-	BAY-94-9172, AV-1	[¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F]AZD4694
Parent molecule	Benzothiazole	Benzothiazole	Styrylpyridine	Stilbene	Benzothiazole
Amyloid affinity (Ki, nM)	0.9	0.7	2.2.	2.4	0.7
Plasma metabolites	Polar	Polar	Polar and non-polar	Polar and non-polar	Polar
Typical injected dose (MBq)	250-450	250-450	300	300	300
Typical imaging time (min)	40-90	90-110	50-70	90-130	50-60

Biological target	Radiotracers	Findings	Typical brain regions involved
Amyloid deposition	[¹¹11. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011;7(3):263-9.C]PIB [¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F]Florbetapir [¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F] Florbetaben [¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F] Flutemetamol [¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F]NAV4694	Increased retention	Frontal cortex, medial and lateral posterior parietal cortices, precuneus Occipital cortex, lateral, temporal cortices and striatum
Tau pathology	[¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F]T807 [¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F]T808 [¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F]THK523 [¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F]THK5105 [¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F]THK5117 [¹¹11. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011;7(3):263-9.C]PBB3	Increased retention	Frontal cortex, temporal cortex, parietal cortex and hippocampus/entorhinal region
Glucose metabolism	[¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F]FDG	Low uptake	Parietotemporal association cortices, medial temporal cortex, posterior cingulate and frontal cortex (at later stages)
Neuroinflammation	[¹¹11. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011;7(3):263-9.C]PK11195 [¹¹11. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011;7(3):263-9.C]DAA1106 [¹⁸18. Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630-45.F]FEDAA1106 [¹¹11. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011;7(3):263-9.C]AC5216 [¹¹11. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011;7(3):263-9.C]A836339 [¹¹11. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011;7(3):263-9.C]L-deprenyl	Increased retention	Widespread retention within the whole brain

Academia Brasileira de Neurologia, Departamento de Neurologia Cognitiva e Envelhecimento R. Vergueiro, 1353 sl.1404 - Ed. Top Towers Offices, Torre Norte, São Paulo, SP, Brazil, CEP 04101-000, Tel.: +55 11 5084-9463 | +55 11 5083-3876 - São Paulo - SP - Brazil
E-mail: revistadementia@abneuro.org.br | demneuropsy@uol.com.br

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[1] Pedro Rosa-Neto. McGill Center for Studies in Aging, 6825 LaSalle Boulevad, Montreal, H4H 1R3 Quebec - Canada. E-mail: ac.lligcm@asor.ordep