Co-expression patterns of microglia markers Iba1, TMEM119 and P2RY12 in Alzheimer's disease

Microglia have been identified as key players in Alzheimer's disease pathogenesis, and other neurodegenerative diseases. Iba1, and more specifically TMEM119 and P2RY12 are gaining ground as presumedly more specific microglia markers, but comprehensive characterization of the expression of these three markers individually as well as combined is currently missing. Here we used a multispectral immunofluorescence dataset, in which over seventy thousand microglia from both aged controls and Alzheimer patients have been analysed for expression of Iba1, TMEM119 and P2RY12 on a single-cell level. For all markers, we studied the overlap and differences in expression patterns and the effect of proximity to β-amyloid plaques. We found no difference in absolute microglia numbers between control and Alzheimer subjects, but the prevalence of specific combinations of markers (phenotypes) differed greatly. In controls, the majority of microglia expressed all three markers. In Alzheimer patients, a significant loss of TMEM119+ phenotypes was observed, independent of the presence of β-amyloid plaques in its proximity. Contrary, phenotypes showing loss of P2RY12, but consistent Iba1 expression were increasingly prevalent around β-amyloid plaques. No morphological features were conclusively associated with loss or gain of any of the markers or any of the identified phenotypes. All in all, none of the three markers were expressed by all microglia, nor can be wholly regarded as a pan- or homeostatic marker, and preferential phenotypes were observed depending on the surrounding pathological or homeostatic environment. This work could help select and interpret microglia markers in previous and future studies.

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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.

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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

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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

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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.

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

ACS Medicinal Chemistry Letters ◽

10.1021/ml100082x ◽

2010 ◽

Vol 1 (7) ◽

pp. 321-325 ◽

Cited By ~ 27

Author(s):

Yan Cheng ◽

Masahiro Ono ◽

Hiroyuki Kimura ◽

Shinya Kagawa ◽

Ryuichi Nishii ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Pet Imaging ◽

Amyloid Plaques ◽

Β Amyloid

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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

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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.

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