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. 2012 Mar 12;3(4):265-7.
doi: 10.1021/ml300058m. eCollection 2012 Apr 12.

The β-Amyloid Hypothesis in Alzheimer's Disease: Seeing Is Believing

Hank F Kung  1
Affiliations

The β-Amyloid Hypothesis in Alzheimer's Disease: Seeing Is Believing

Hank F Kung. ACS Med Chem Lett. .
No abstract available

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Figures

Figure 1
Figure 1
(A) Simplified model of the excessive Aβ peptide production leading to the formation of Aβ plaques. Normally, amyloid precursor protein (APP) of neurons is metabolized by three proteases (α-, β-, and γ-secretases). Increasing production or decreasing clearance of Aβ peptides leads to the formation of Aβ aggregates in the brain. The fibrillar aggregates of amyloid peptides, mainly Aβ40 and Aβ42 (in green), are major metabolic peptides found in the Aβ plaques, and they are believed to be responsible for initiating a cascade of events leading to neurotoxicity and AD. (B) Aβ hypothesis suggests that Aβ peptides participate in AD pathogenesis. The peptides, produced by neurons and other brain cells, stick together like glue and aggregate (formation of β-sheet structures) into a variety of toxic assemblies, neurofibrillary tangles, and neuritic plaques.
Figure 2
Figure 2
(A) Four Aβ imaging agents have been studied in humans. The success in using [11C]PIB for imaging Aβ plaques in the brain has provided considerable impetus for further refinement of this PET imaging technique. [11C]PIB (T1/2 = 20 min) has limitations (requires an on-site cyclotron and a radiochemistry team). Additional tracers labeled with 18F (T1/2 = 110 min) for Aβ imaging were developed. Using 18F PET agents, the manufacturing and distribution can be centralized, which will significantly simplify the clinical application. Currently, the final FDA approval of florbetapir f18 (Amyvid) is pending; flutemetamol f18 and florbetaben f18 are under phase II clinical trials. (B) Paired representative florbetapir f18-PET scans in living human brain and Aβ antibody immunohistochemistry staining of comparable postmortem brain sections. PET scans and antibody staining of representative brain sections are shown: (A) Normal control (no Aβ plaques), (B) moderate level of Aβ plaques, and (C) high level of Aβ plaques. Reproduced with permission from ref (3). Copyright 2011 American Medical Association.
See this image and copyright information in PMC

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