Fluorinated Benzofuran Derivatives for PET Imaging of β-Amyloid Plaques in Alzheimer's Disease Brains

AbstractAlzheimer's disease is a degenerative neurological condition characterized by the presence of β-amyloid plaques and neurofibrillary tangles in the limbic and neocortical regions of the brain. Pittsburgh Compound-B (PIB), a benzothiazole analog, has recently been found to specifically label amyloid deposits in positron emission tomography (PET) studies of the brain, opening the door for a wide range of applications related to Alzheimer's disease. In this article, data demonstrating the specificity of PIB as a PET tracer for β-amyloid lesions are reviewed, and the potential clinical applications of PIB PET imaging is discussed. Because amyloid plaques are common even in elderly individuals who are not suffering from dementia, the primary diagnostic function of PIB PET imaging presumably would be to rule out, rather than definitively confirm, Alzheimer's diagnoses in elderly patients. Other possible uses include monitoring plaque loads in patients receiving anti-amyloid therapy for Alzheimer's disease, as well as assessing plaque formation in unaffected individuals as a means of evaluating future Alzheimer's disease.

Download Full-text

Synthesis of a Novel Curcumin Derivative as a Potential Imaging Probe in Alzheimer’s Disease Imaging

Current Alzheimer Research ◽

10.2174/1567205016666190816130516 ◽

2019 ◽

Vol 16 (8) ◽

pp. 723-731 ◽

Cited By ~ 1

Author(s):

Alexander Sturzu ◽

Sumbla Sheikh ◽

Hubert Kalbacher ◽

Thomas Nägele ◽

Christopher Weidenmaier ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Flow Cytometry ◽

Transgenic Mice ◽

Ex Vivo ◽

Amyloid Plaques ◽

Laser Scanning Microscopy ◽

Β Amyloid ◽

Curcumin Derivative

Background: Curcumin has been of interest in the field of Alzheimer’s disease. Early studies on transgenic mice showed promising results in the reduction of amyloid plaques.However, curcumin is very poorly soluble in aqueous solutions and not easily accessible to coupling as it contains only phenolic groups as potential coupling sites. For these reasons only few imaging studies using curcumin bound as an ester were performed and curcumin is mainly used as nutritional supplement. Methods: In the present study we produced an aminoethyl ether derivative of curcumin using a nucleophilic substitution reaction. This is a small modification and should not impact the properties of curcumin while introducing an easily accessible reactive amino group. This novel compound could be used to couple curcumin to other molecules using the standard methods of peptide synthesis. We studied the aminoethyl-curcumin compound and a tripeptide carrying this aminoethyl-curcumin and the fluorescent dye fluorescein (FITC-curcumin) in vitro on cell culture using confocal laser scanning microscopy and flow cytometry. Then these two substances were tested ex vivo on brain sections prepared from transgenic mice depicting Alzheimer-like β-amyloid plaques. Results: In the in vitro CLSM microscopy and flow cytometry experiments we found dot-like unspecific uptake and only slight cytotoxicity correlating with this uptake. As these measurements were optimized for the use of fluorescein as dye we found that the curcumin at 488nm fluorescence excitation was not strong enough to use it as a fluorescence marker in these applications. In the ex vivo sections CLSM experiments both the aminoethyl-curcumin and the FITC-curcumin peptide bound specifically to β- amyloid plaques. Conclusion: In conclusion we successfully produced a novel curcumin derivative which could easily be coupled to other imaging or therapeutic molecules as a sensor for amyloid plaques.

Download Full-text

Development of Phenothiazine-Based Theranostic Compounds That Act Both as Inhibitors of β-Amyloid Aggregation and as Imaging Probes for Amyloid Plaques in Alzheimer’s Disease

ACS Chemical Neuroscience ◽

10.1021/acschemneuro.6b00380 ◽

2017 ◽

Vol 8 (4) ◽

pp. 798-806 ◽

Cited By ~ 17

Author(s):

Pascal Dao ◽

Feifei Ye ◽

Yan Liu ◽

Zhi Yun Du ◽

Kun Zhang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Plaques ◽

Amyloid Aggregation ◽

Imaging Probes ◽

Β Amyloid

Download Full-text

Development of Novel 123I-Labeled Pyridyl Benzofuran Derivatives for SPECT Imaging of β-Amyloid Plaques in Alzheimer’s Disease

PLoS ONE ◽

10.1371/journal.pone.0074104 ◽

2013 ◽

Vol 8 (9) ◽

pp. e74104 ◽

Cited By ~ 24

Author(s):

Masahiro Ono ◽

Yan Cheng ◽

Hiroyuki Kimura ◽

Hiroyuki Watanabe ◽

Kenji Matsumura ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Plaques ◽

Spect Imaging ◽

Β Amyloid

Download Full-text

Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau

10.21203/rs.3.rs-101153/v2 ◽

2021 ◽

Author(s):

Niklas Mattsson-Carlgren ◽

Shorena Janelidze ◽

Randall Bateman ◽

Ruben Smith ◽

Erik Stomrud ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Medial Temporal Lobe ◽

Amyloid Plaques ◽

Amyloid Plaque ◽

Amyloid Pet ◽

Tau Pathology ◽

Β Amyloid ◽

Tau Pet ◽

Disease Stages

Abstract Alzheimer’s disease is characterized by β-amyloid plaques and tau tangles. Plasma levels of phospho-tau217 (P-tau217) accurately differentiate Alzheimer’s disease dementia from other dementias, but it is unclear to what degree this reflects β-amyloid plaque accumulation, tau tangle accumulation, or both. In a cohort with post-mortem neuropathological data (N=88), both plaque and tangle density contributed independently to higher P-tau217. Several findings were replicated in a cohort with PET imaging (“BioFINDER-2”, N=426), where β-amyloid and tau PET were independently associated to P-tau217. P-tau217 correlated with β-amyloid PET (but not tau PET) in early disease stages, and with both β-amyloid and (more strongly) tau PET in late disease stages. Finally, P-tau217 mediated the association between β-amyloid and tau in both cohorts, especially for tau outside of the medial temporal lobe. These findings support the hypothesis that plasma P-tau217 is increased by both β-amyloid plaques and tau tangles and is congruent with the hypothesis that P-tau is involved in β-amyloid-dependent formation of neocortical tau tangles.

Download Full-text

Migration of blood cells to β-amyloid plaques in Alzheimer's disease

Experimental Gerontology ◽

10.1016/j.exger.2015.03.002 ◽

2015 ◽

Vol 65 ◽

pp. 8-15 ◽

Cited By ~ 41

Author(s):

Lindsay A. Hohsfield ◽

Christian Humpel

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Blood Cells ◽

Amyloid Plaques ◽

Β Amyloid

Download Full-text

Role of Cofilin in Alzheimer’s Disease

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.584898 ◽

2020 ◽

Vol 8 ◽

Author(s):

Qiang Wang ◽

Wei Yuan ◽

Xiaohang Yang ◽

Yuan Wang ◽

Yongfeng Li ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Plaques ◽

Executive Dysfunction ◽

Actin Binding ◽

Synaptic Dysfunction ◽

Hyperphosphorylated Tau ◽

Hirano Bodies ◽

Visual Spatial ◽

Β Amyloid

Alzheimer’s disease (AD) is a degenerative neurological disease and has an inconspicuous onset and progressive development. Clinically, it is characterized by severe dementia manifestations, including memory impairment, aphasia, apraxia, loss of recognition, impairment of visual-spatial skills, executive dysfunction, and changes in personality and behavior. Its etiology is unknown to date. However, several cellular biological signatures of AD have been identified such as synaptic dysfunction, β-amyloid plaques, hyperphosphorylated tau, cofilin-actin rods, and Hirano bodies which are related to the actin cytoskeleton. Cofilin is one of the most affluent and common actin-binding proteins and plays a role in cell motility, migration, shape, and metabolism. They also play an important role in severing actin filament, nucleating, depolymerizing, and bundling activities. In this review, we summarize the structure of cofilins and their functional and regulating roles, focusing on the synaptic dysfunction, β-amyloid plaques, hyperphosphorylated tau, cofilin-actin rods, and Hirano bodies of AD.

Download Full-text