Chapter 20 Neuropathological hallmarks of Alzheimer's and Parkinson's diseases

Braak, Heiko; Vos, R A de; Jansen, E. N. H.; Bratzke, H.; Braak, Eva

doi:10.1016/s0079-6123(08)64021-2

Cited by 129 publications

(87 citation statements)

References 64 publications

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“…This shows that the decreased immunostaining was caused either by the diminished immunoreactivity or by selective disappearance of neurons. These alternatives are in accordance with other reports, since the affected neurons, although severely damaged, can survive for a long time before they eventually die (28).…”

Section: Discussionsupporting

confidence: 93%

“…One of the characteristic features of AD is that only specific types of neurons are affected by the neuropathological changes, whereas other, sometimes adjoining, cell types remain undamaged or exhibit only secondary injury (28,29). These affected neurons may be particularly vulnerable to cell death because they possess receptors through which the degenerative processes can be triggered.…”

Section: Discussionmentioning

confidence: 99%

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Complement C5a Receptor-Mediated Signaling May Be Involved in Neurodegeneration in Alzheimer’s Disease

Farkas

Takahashi

Fukuda

et al. 2003

The Journal of Immunology

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In our earlier results, we demonstrated that cells expressing the complement C5aR are vulnerable since abnormal activation of C5aR caused apoptosis of these cells. In this study, we demonstrate that activation of C5aR by antisense homology box (AHB) peptides synthesized in multiple antigenic peptide form and representing putative interaction sites of the C5a/C5aR evoked calcium influx in TGW neuroblastoma cells. Dose-dependent inhibition of the response was found when the cells were pretreated with C5a, suggesting that C5aR was involved in this process. In addition, pretreatment with monomeric forms of the AHB peptides resulted in attenuation of the calcium signals, supporting the idea of the role of C5aR in this process. Cells of a neuron-rich primary culture and pyramidal cells of rat brain slices also responded to the AHB peptide activation with an increase in the intracellular calcium level, showing that calcium metabolism might be affected in these cells. TUNEL staining demonstrated that C5aR-mediated apoptosis could be induced both in cells of the primary culture as well as in cortical pyramidal neurons of the rat brain. In addition, we investigated expression of C5aR in the hippocampal and cortical neurons of human brains of healthy and demented patients using two anti-human C5aR Abs. Pyramidal cells of the hippocampus and cortex and granular cells of the hippocampus were immunopositive on staining. Although staining was also positive in the vascular dementia brain, it disappeared in the brain with Alzheimer’s disease. These results provide further support that C5aR may be involved in neurodegeneration.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Complement C5a Receptor-Mediated Signaling May Be Involved in Neurodegeneration in Alzheimer’s Disease

Farkas

Takahashi

Fukuda

et al. 2003

The Journal of Immunology

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“…In our sample, there was negative or very week correlation between DED slope/intercept values and age in our control group, examined in the four cortical regions which showed statistically significant increase in DED binding between patients and controls The pattern of DED binding is well in accordance with what is expected from neuropathological findings. Elevated DED levels were found only in cortex, the main area of neuritic plaque deposition at neuropathological examination [36]. Also cortical regions affected by high neuritic plaque deposition, i.e.…”

Section: Discussionmentioning

confidence: 91%

In vivo imaging of astrocytosis in Alzheimer’s disease: an 11C-L-deuteriodeprenyl and PIB PET study

Santillo

Gambini

Lannfelt

et al. 2011

Eur J Nucl Med Mol Imaging

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“…Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia [1,2]. The disease is characterized by extracellular accumulation of senile plaques, mainly composed of aggregated forms of the amyloid-beta peptide (Aβ), as well as intracellular accumulation of neurofibrillary tangles of the microtubule-associated protein tau [1].…”

Section: Alzheimer's Disease: the Cholinergic System As A Therapeuticmentioning

confidence: 99%

Cotinine: A Potential New Therapeutic Agent against Alzheimer's disease

Echeverrı́a

Zeitlin

2012

CNS Neuroscience & Therapeutics

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SUMMARYTobacco smoking has been correlated with a lower incidence of Alzheimer's disease (AD). This negative correlation has been attributed to nicotine's properties. However, the undesired side-effects of nicotine and the absence of clear evidence of positive effects of this drug on the cognitive abilities of AD patients have decreased the enthusiasm for its therapeutic use. In this review, we discuss evidence showing that cotinine, the main metabolite of nicotine, has many of the beneficial effects but none of the negative side-effects of its precursor. Cotinine has been shown to be neuroprotective, to improve memory in primates as well as to prevent memory loss, and to lower amyloid-beta (Aβ)) burden in AD mice. In AD, cotinine's positive effect on memory is associated with the inhibition of Aβ aggregation, the stimulation of pro-survival factors such as Akt, and the inhibition of pro-apoptotic factors such as glycogen synthase kinase 3 beta (GSK3β). Because stimulation of the α7 nicotinic acetylcholine receptors (α7nAChRs) positively modulates these factors and memory, the involvement of these receptors in cotinine's effects are discussed. Because of its beneficial effects on brain function, good safety profile, and nonaddictive properties, cotinine may represent a new therapeutic agent against AD. Alzheimer's disease: The Cholinergic System as a Therapeutic TargetAlzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia [1,2]. The disease is characterized by extracellular accumulation of senile plaques, mainly composed of aggregated forms of the amyloid-beta peptide (Aβ), as well as intracellular accumulation of neurofibrillary tangles of the microtubule-associated protein tau [1]. These neuropathological changes are associated with structural brain abnormalities, inflammation, and cognitive impairment such as impairment of working memory in AD patients. The progressive loss of memory in AD patients correlates with increased levels of Aβ and the deterioration of the cholinergic system in the brain. The degenerative process involves a sequence of pathological events, including early degeneration of the cerebral basal forebrain and subsequent deterioration of the cortical cholinergic system [3,4]. This deterioration commonly includes a reduction in the levels of acetylcholine (ACh) and α3, α4, and α7 nicotinic ACh receptors (nAChRs) as well as a decrease in the activity of choline acetyltranferase in the brain [5].Of these nAChRs, the α7 receptors are considered to be ideal therapeutic targets for several neurological conditions, including AD, schizophrenia, and Parkinson's disease (PD) as well as tobacco addiction [6,7]. The α7nAChR is a homomeric pentamer that has a high permeability to calcium (P Ca :P Na ≈ 10), and undergoes rapid and reversible desensitization and pronounced inward rectification [8]. The α7 subunit is highly expressed in the cortex, hippocampus, and hypothalamus [8], and has also been suggested to have functionally important expression in ...

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Chapter 20 Neuropathological hallmarks of Alzheimer's and Parkinson's diseases

Cited by 129 publications

References 64 publications

Complement C5a Receptor-Mediated Signaling May Be Involved in Neurodegeneration in Alzheimer’s Disease

Complement C5a Receptor-Mediated Signaling May Be Involved in Neurodegeneration in Alzheimer’s Disease

In vivo imaging of astrocytosis in Alzheimer’s disease: an 11C-L-deuteriodeprenyl and PIB PET study

Cotinine: A Potential New Therapeutic Agent against Alzheimer's disease

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