Extraneural cholinergic markers in Alzheimer's and Parkinson's disease

Muscarinic and nicotinic binding sites were analysed in lymphocytes from patients with Alzheimer's disease, Multi-infarct dementia, Parkinson's disease and age- matched controls. A significant decrease in the number of both muscarinic and nicotinic binding sites was obtained in lymphocytes from Alzheimer patients while in Parkinson patients a significant decrease was found only in the nicotinic binding sites. Using butyrylthiocholine as substrate, no change was observed in cholinesterase activity in plasma from Alzheimer patients, whereas a significant decrease in plasma cholinesterase activity was found in Parkinson patients.     

In vivo mapping of cholinergic terminals in normal aging,Alzheimer's disease,and Parkinson's disease

To map presynaptic cholinergic terminal densities in normal aging (n = 36), Alzheimer's disease (AD) (n = 22), and Parkinson's disease (PD) (n = 15), we performed single-photon emission computed tomography using [¹²³I]iodoben-zovesamicol (IBVM), an in vivo marker of the vesicular acetylcholine transporter. We used coregistered positron emission tomography with [¹⁸F]fluorodexyglucose for metabolic assessment and coregistered magnetic resonance imaging for atrophy assessment. In controls (age, 22–91 years), cortical IBVM binding declined only 3.7% per decade. In AD, cortical binding correlated inversely with dementia severity. In mild dementia, binding differed according to age of onset, but metabolism did not. With an onset age of less than 65 years, binding was reduced severely throughout the entire cerebral cortex and hippocapus (about 30%), but with an onset age of 65 years or more, binding reductions were restricted to temporal cortex and hippocampus. In PD without dementia, binding was reduced only in parietal and occipital cortex, but demented PD subjects had extensive cortical binding decreases similar to early-onset AD. We conclude that cholinergic neuron integrity can be monitored in living AD and PD patients, and that it is not so devastated in vivo as suggested by postmortem choline acetylransferase activity (50–80%).     

帕金森病与阿尔茨海默病

普遍认为帕金森病和阿尔茨海默病是两个独立的、有着显著差别的疾病.但是,相当数量的证据表明,二者具有相互重叠的临床和神经病理特征、相似的病因和病变发生机制.因此,现在有人认为这两种疾病的部分病例可能是同一种神经元退行性变疾病的不同表现形式.本文拟对此作一介绍.     

帕金森病与阿尔茨海默病

普遍认为帕金森病和阿尔茨海默病是两个独立的、有着显著判别的疾病。但是,相当数量为证据表明,二者具有相互重叠的临床和神经病理特征、相似的病因和病变发生机制。因此,现在有人认为这两种疾病的部分病例可能是同一种神经元退行性变疾病的不同表现形式。本文拟对此作一介绍。     

Glycation in Parkinson's disease and Alzheimer's disease

Glycation is a spontaneous age‐dependent posttranslational modification that can impact the structure and function of several proteins. Interestingly, glycation can be detected at the periphery of Lewy bodies in the brain in Parkinson's disease. Moreover, α‐synuclein can be glycated, at least under experimental conditions. In Alzheimer's disease, glycation of amyloid β peptide exacerbates its toxicity and contributes to neurodegeneration. Recent studies establish diabetes mellitus as a risk factor for several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. However, the mechanisms underlying this connection remain unclear. We hypothesize that hyperglycemia might play an important role in the development of these disorders, possibly by also inducing protein glycation and thereby dysfunction, aggregation, and deposition. Here, we explore protein glycation as a common player in Parkinson's and Alzheimer's diseases and propose it may constitute a novel target for the development of strategies for neuroprotective therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society     

Alzheimer's disease affects limbic nuclei of the thalamus

Summary Sensitive silver techniques for amyloid and neurofibrillary changes were applied to examine the pathological changes revealed by limbic nuclei of the thalamus in Alzheimer's disease. Large numbers of extracellular amyloid deposits occurred in almost all thalamic nuclei. The antero-ventral nucleus harbored numerous large globular patches, other areas contained more densely packed and smaller deposits, while narrow zones of gray matter subjacent to the ependymal lining of the third ventricle remained virtually devoid of amyloid. Intraneuronal neurofibrillary changes were encountered in the form of distended argyrophilic processes covering the medial convexity of the antero-ventral nucleus. Similar structures, although in considerably lesser density, occurred in the laterally adjoining reticular nucleus. The anterior nuclear complex, the latero-dorsal nucleus, portions of the intralaminar complex, the paraventricular and reuniens nucleus contained numerous neurofibrillary tangles and neuropil threads. The antero-dorsal nucleus showed the most severe involvement. At first glance, the thalamus appeared to be only mildly affected by Alzheimer's disease. Closer inspection revealed that severe changes were confined to only a few limbic nuclei. These changes were virtually identical in amount, type and location in all cases of severe Alzheimer's disease studied. It is assumed that these changes considerably hamper the transport of information through limbic circuits.Supported by the Deutsche Forschungsgemeinschaft     

Aminergic systems in Alzheimer's disease and Parkinson's disease

Biochemical markers for serotoninergic and catecholaminergic neurons in frontal and temporal poles were examined post mortem in brains of patients with Alzheimer's disease, Parkinson's disease, and the two combined. Binding of [3H] citalopram to serotoninergic uptake sites and levels of serotonin were decreased by 40 to 50% in brains of persons in each disease category. In contrast, significant reductions of catecholaminergic markers were not detected. In all three disease groups, the choline acetyltransferase activity was reduced by 50 to 60%. Binding sites for adenosine (A1), muscarinic cholinergic, phencyclidine, beta-adrenergic, and calcium antagonist receptors were unchanged. We conclude that substantial damage to serotoninergic neurons occurs in persons with Parkinson's and Alzheimer's diseases.     

Parkinson's disease in patients with Alzheimer's disease

Because patients with Alzheimer's disease often develop clinical manifestations of Parkinson's disease, we examined the substantia nigra in 40 cases of pathologically confirmed Alzheimer's disease for the changes of Parkinson's disease (neuronal loss, Lewy bodies, or neurofibrillary tangles). Eighteen patients had one or more of these changes in the substantia nigra. Subsequently, we reviewed their clinical records and found that rigidity, with or without tremor, had been noted in 13 patients, and nine patients had a second diagnosis of possible or definite Parkinson's disease. Eleven (85%) of these patients had the pathologic changes of Parkinson's disease. These findings suggest that the majority of patients with Alzheimer's disease with extrapyramidal signs have the pathologic changes of Parkinson's disease in the substantia nigra.     

PET studies and cholinergic therapy in Alzheimer's disease

Alzheimer's disease (AD) is one of the most devastating brain disorders of elderly humans. The last decade has witnessed a steadily increasing effort directed at discovery of the etiology of the disease and development of pharmacological treatment stategies. Symptomatic treatment mainly focussing on cholinergic therapy has been clinical evaluated by randomized, double-blind, placebo controlled, parallel group studies measuring performance based tests of cognitive function, activity of daily living and behavior. Significant progress has been made in recent years to develop and apply functional brain imaging techniques allowing early diagnosis of dementia and evaluation of treatment efficacy. Positron emission tomography (PET) is a suitable method for functional studies of pathological changes in brain which as a clinical instrument not solely reveal dysfunctional changes early in the course of the disease but also may provide a deep insight into the functional mechanisms of new potential drug treatment strategies. The advantage with PET is the capacity not only to measure changes in glucose metabolism, cerebral blood flow but also to obtain further insight into neuronal communicative processes (transmitter/receptor interactions) in brain and pharmacokinetic events and drug mechanisms. PET studies have so far revealed disturbances in some neuroreceptor systems in brain of AD patients. A significant correlation can be observed between the impairment of nicotinic receptors in the temporal cortex and the cognitive impairment of AD patients. Cholinergic drugs including cholinesterase inhibitors such as physostigmine, tacrine, velnacrine as well as the acetylcholine releaser linopiridine have been reported to increase the cerebral blood flow in AD patients both after acute and fairly short period of treatment. Increase in cerebral glucose metabolism has also been measured following fairly long periods of treatment with cholinesterase inhibitors (months). The cholinergic nicotinic and muscarinic receptors do also respond to treatment with cholinesterase inhibitors in AD patients. An improvement of the nicotinic receptors has been found in cortical regions following treatment with cholinesterase inhibitors and nerve growth factors (NGF) to AD patients. Functional PET activation studies performed simultaneously with memory tasks will provide further valuable insight into the mechanisms of action of new drug, how they interact and can improve the efficacy of memory processes in AD brains.     

阿尔茨海默病早期的胆碱能系统成像进展

阿尔茨海默病(Alzheimer's disease, AD)患者脑内神经递质代谢障碍是其重要的病理特征,其中胆碱能损伤学说目前较为公认,AD患者皮质的胆碱能系统发生严重退变,引起学习记忆减退和认知障碍,从而产生痴呆症状.近年来,胆碱能系统等关键部位活体成像技术已经成熟,并已经开始应用于AD的极早期阶段.目前初步的结果显示,AD的早期损害包括有乙酰胆碱转运体的减少、乙酰胆碱酯酶含量的降低及突触前乙酰胆碱受体数目的减少.现就近年来对AD早期的胆碱能系统成像进展做一综述.     

The rostral mesencephalon in Parkinson's disease and Alzheimer's disease

Summary The rostal mesencephalon at the level of the posterior commissure was studied by light microscopy in two patients with idiopathic Parkinson's disease, one patient with Alzheimer's disease, and one patient with senile dementia of Alzheimer's type. In the Parkinsonian cases, the rostral part of the nucleus of Edinger Westphal disclosed Lewy bodies in 3% of the neurons, neurofibrillary degeneration in 2% of the neurons, and a 54% neuronal loss. In Alzheimer's disease, 2% of Edinger Westphal neurons contained neurofibrillary degeneration, whereas in senile dementia of Alzheimer's type only rare neurofibrillary degeneration was evident in this nucleus. Neuronal loss was not apparent in the nucleus of Edinger Westphal in either of the Alzheimer's cases. The pathologic changes observed in this presumably cholinergic nucleus resemble in some respects changes reported in the cholinergic centers of the basal forebrain in these diseases.In addition, the central gray matter and pretectal region in Parkinson's disease contained a patchy increase in astroglia, some with scant reactive cell bodies; however, Lewy bodies were limited to that part of the central gray matter corresponding to the nucleus of Darkschewitsch. A few neurofibrillary tangles were present in the nucleus of Darkschewitsch in both diseases.     

Alzheimer's disease and Parkinson's disease: neuropsychological differentiation

54 patients with idiopathic Parkinson's disease (PD), 26 patients with Alzheimer's disease (AD) and 18 control subjects, all over 55, have performed neuropsychological tests, evaluating global intellectual function (Rosen's cognitive scale, WAIS digit symbol, WAIS similitude and WMS logical memory tests) and visuospatial functions (Rey lacunar pictures, Poppelreuter and Benton line orientation tests). AD group results were distinctly different from those of the PD and the control groups (p less than 0.001). In the PD group, only the Rosen's scale total score and the visuospatial tests were slightly altered (p less than 0.05). In a PD subgroup with a normal Rosen's scale result, the Benton line orientation test was different from controls (p less than 0.05). In another PD subgroup with Rosen's scale score comparable to a midly impaired AD subgroup, all the neuropsychological tests were abnormal. Only the WAIS digit symbol test, altered in this PD subgroup, was different comparing these 2 subgroups (p less than 0.05). With regard to the PD total group, the neuropsychological perturbed PD subgroup was older, had a longer duration of disease, a higher depression's score, less tremor and a worse equilibrium. These results might reflect a neuropsychological defect heterogeneity among PD patients, related to various pathophysiological hypothesis which are discussed in this paper.     

Alpha-synuclein, Parkinson's disease, and Alzheimer's disease

Alpha synuclein (alpha-SN) is a ubiquitous protein that is especially abundant in the brain and has been postulated to play a central role in the pathogenesis of Parkinson's disease (PD), Alzheimer's disease, and other neurodegenerative disorders. Here, we show that alpha-SN plays dual role of neuroprotection and neurotoxicity depending on its concentration or level of expression. In addition, our study shows that alpha-synuclein is differentially expressed in human peripheral blood mononuclear cells. PD patients expressed more alpha-synuclein than healthy controls. Thus, the alpha-synuclein expression in the peripheral immune system might be one of the primary causes of immune abnormalities in PD patients.     

Implicit and explicit memory in Alzheimer's disease and Parkinson's disease

Abstract

Several tasks examined implicit and explicit memory in demographically matched samples of Alzheimer's (AD) and Parkinson's disease (PD) patients, and healthy elderly subjects. A fragmented pictures test, word stem-completion repetition priming, and a pursuit-rotor tracking task, followed by explicit memory tests, were given. AD patients were impaired on all explicit tests and on word stem-completion priming, but were intact on pursuit-rotor tracking and the skill learning (SL) component of the fragmented pictures test. PD patients were significantly better than AD patients on all explicit memory tests, but were selectively impaired on the SL component of the fragmented pictures test. Finally, a mirror-reading test was given to the PD patients and control subjects, with no significant differences found in performances between the two groups. Results are discussed in terms of hypothetical cognitive processes and brain circuits underlying different implicit and explicit memory domains.     

Implicit and explicit memory in Alzheimer's disease and Parkinson's disease

Several tasks examined implicit and explicit memory in demographically matched samples of Alzheimer's (AD) and Parkinson's disease (PD) patients, and healthy elderly subjects. A fragmented pictures test, word stem-completion repetition priming, and a pursuit-rotor tracking task, followed by explicit memory tests, were given. AD patients were impaired on all explicit tests and on word stem-completion priming, but were intact on pursuit-rotor tracking and the skill learning (SL) component of the fragmented pictures test. PD patients were significantly better than AD patients on all explicit memory tests, but were selectively impaired on the SL component of the fragmented pictures test. Finally, a mirror-reading test was given to the PD patients and control subjects, with no significant differences found in performances between the two groups. Results are discussed in terms of hypothetical cognitive processes and brain circuits underlying different implicit and explicit memory domains.