Brain capillaries in Alzheimer's disease.

Alzheimer's disease is the most common cause of irreversible dementia, affecting mostly the presenile and senile age, shaping a tragic profile in the epilogue of the life of the suffering people. Due to the severity and the social impact of the disease an ongoing research activity is in climax nowadays, associated with many legal, social, ethical, humanitarian, philosophical and economic considerations. From the neuropathological point of view the disease is characterized by dendritic pathology, loss of synapses and dendritic spines, affecting mostly selective neuronal networks of critical importance for memory and cognition, such as the basal forebrain cholinergic system, the medial temporal regions, the hippocampus and many neocortical association areas. Tau pathology consisted of intracellular accumulation of neurofibrillary tangles of hyperphosphorilated tau protein and accumulation of Aß-peptide's deposits, defined as neuritic plaques, are the principal neuropathological diagnostic criteria of the disease. The neurotoxic properties of the oligomerics of the Aß-peptide and tau mediated neurodegeneration are among the main causative factors of impaired synaptic plasticity, neuronal loss, dendritic alterations and tremendous synaptic loss. The gradual degeneration of the organelles, particularly mitochondria, smooth endoplasmic reticulum and Golgi apparatus, visualized clearly by electron microscopy (EM), emphasize the importance of the oxidative stress and amyloid toxicity in the pathogenetic cascade of the disease. The vascular factor may be an important component of the whole spectrum of the pathogenesis of AD. It is of substantial importance the concept that the structural alterations of the brain capillaries, may contribute in the pathology of AD, given that the disruption of the BBB may induce exacerbation of AD pathology, by promoting inflammation around the blood capillaries and in the neuropile space diffusely. From the morphological point of view, silver impregnation techniques revealed a marked tortuosity of the capillaries in early cases of AD. In addition, the distance between two branch points is longer in capillaries of AD brains, whereas the branch point density as well as the ratio of the branch point density to astrocytic density is substantially decreased in AD in comparison with age matched normal controls. EM revealed, that the most frequent morphological alterations of the brain capillaries in AD consist of thickness, splitting and duplication of the basement membrane, reduction of the length of tight junctions, decrease of the number of tight junctions per vessel length, associated as a rule, with morphological alterations of the mitochondria of the endothelial cells, the pericytes and the perivascular astrocytic processes. The number of the pinocytotic vesicles is substantially increase in the endothelium of the brain capillaries in AD in comparison with age matched normal controls. Endothelial cells play a very important role in the transport systems in the brain. Subsequently, the dysfunction of the endothelial cells and the disruption of the BBB may induce serious impairment in the transport system. The dysfunction of the brain capillaries may result in releasing neurotoxic factors, such as thrombin, pro-inflammatory cytokines, nitric oxide and leukocyte adhesion molecules, and in abnormal regulation of Aß-peptide homeostasis in the brain. The impairment of the brain capillaries in structures of the brain, which are crucial for the homeostatic equilibrium, such as the hypothalamic nuclei, may induce autonomic dysfunction, which usually occur in the advanced stages of AD, affecting dramatically the viability of the patients. Degeneration of the pericytes is also observed emphasizing even more the importance of the vascular factor in AD. Pericytes may serve as integrators, coordinators and effectors of blood-brain barrier structure and maintenance, and play a key role in microvascular stability, capillary density and angiogenesis. The correlation between AD pathology and vascular pathology, at the level of brain capillaries and BBB, raises the rational question, whether the efficient treatment of the vascular factor might be beneficial for the patients who suffer from AD. It is reasonable that any protection of the brain capillaries at the initial stages of the disease might contribute in the abbreviation of the long chain of pathological alteration, which occur following the disruption of the BBB, which serves as the essential interface between the vascular system and the brain.

Epilepsy, behavior, and art (Epilepsy, Brain, and Mind, part 1).

Epilepsy is both a disease of the brain and the mind. Brain diseases, structural and/or functional, underlie the appearance of epilepsy, but the notion of epilepsy is larger and cannot be reduced exclusively to the brain. We can therefore look at epilepsy from two angles. The first perspective is intrinsic: the etiology and pathophysiology, problems of therapy, impact on the brain networks, and the "mind" aspects of brain functions - cognitive, emotional, and affective. The second perspective is extrinsic: the social interactions of the person with epilepsy, the influence of the surrounding environment, and the influences of epilepsy on society. All these aspects reaching far beyond the pure biological nature of epilepsy have been the topics of two International Congresses of Epilepsy, Brain, and Mind that were held in Prague, Czech Republic, in 2010 and 2012 (the third Congress will be held in Brno, Czech Republic on April 3-5, 2014; www.epilepsy-brain-mind2014.eu). Here, we present the first of two papers with extended summaries of selected presentations of the 2012 Congress that focused on epilepsy, behavior, and art.

Dendritic and spinal pathology of the Purkinje cells from the human cerebellar vermis in Alzheimer's disease.

BACKGROUND: Alzheimer's disease constitutes one of the main causes of dementia. It is clinically characterized by memory impairment, deterioration of intellectual faculties and loss of professional skills. Furthermore changes in equilibrium and limb coordination are clinically demonstrable in persons with Alzheimer's disease. In the present study we tried to figure out possible changes of the Purkinje cells in Alzheimer's disease brains. SUBJECTS AND METHODS: We studied the Purkinje cells from the vermis of the cerebellum in 5 Alzheimer' disease brains Golgi technique. RESULTS: In the Purkinje cells from the inferior surface of the cerebellar hemispheres severe dendritic and spinal pathology consisting of loss of distal dendritic segments and alterations of dendritic spine morphology can be noticed in Alzheimer's disease brains. CONCLUSIONS: The morphological and morphometric estimation of the dendrites and the dendritic spines of the Purkinje cells from the inferior surface of the cerebellar hemispheres in Alzheimer's disease brains revealed substantial alterations of the dendritic arborization and marked loss of the dendritic spines, which may be related to cognitive impairment and motor deficits in Alzheimer's disease.

Coronaviruses and their relationship with multiple sclerosis: is the prevalence of multiple sclerosis going to increase after the Covid-19 pandemia?

The purpose of this review is to examine whether there is a possible (etiological/triggering) relationship between infection with various Coronaviruses, including Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2), the virus responsible for the Coronavirus disease-19 (Covid-19) pandemia, and Multiple Sclerosis (MS), and whether an increase of the prevalence of MS after the current Covid-19 pandemia should be expected, examining new and preexisting data. Although the exact pathogenesis of MS remains unknown, environmental agents seem to greatly influence the onset of the disease, with viruses being the most popular candidate. Existing data support this possible etiological relationship between viruses and MS, and experimental studies show that Coronaviruses can actually induce an MS-like demyelinating disease in animal models. Findings in MS patients could also be compatible with this coronaviral MS hypothesis. More importantly, current data from the Covid-19 pandemia show that SARS-CoV-2 can trigger autoimmunity and possibly induce autoimmune diseases, in the Central Nervous System as well, strengthening the viral hypothesis of MS. If we accept that Coronaviruses can induce MS, it is reasonable to expect an increase in the prevalence of MS after the Covid-19 pandemia. This knowledge is of great importance in order to protect the aging groups that are more vulnerable against autoimmune diseases and MS specifically, and to establish proper vaccination and health policies.

Morphological and morphometric changes in the Purkinje cells of patients with essential tremor.

Essential tremor (ET) is a progressive neurological syndrome characterised by involuntary tremors of the hands or arms, head, jaw and voice. The pathophysiology of ET is not clearly understood yet. However, previous studies have reported several changes in the brain of patients with ET. One of the brain areas extensively investigated is the cerebellum. In the present study, a morphometric analysis of Purkinje cells in patients with ET and ET-plus was performed, and subsequently compared with normal controls using the Golgi silver staining method and 3D neuronal reconstruction. Substantial morphological changes were uncovered in the Purkinje cells of patients with ET compared with normal controls, including a decreased dendritic length and field density, an overall loss of terminal branches and a decreased density of dendritic spines.

Dendritic pathology and spinal loss in the visual cortex in Alzheimer's disease: a Golgi study in pathology.

Alzheimer's disease is a neurodegenerative disorder characterized by progressive decline in memory, loss of professional skills, impairment of judgement and behavior, and decline in social performances. In terms of neuropathology, the morphological hallmarks of the disease are the accumulation of alpha-beta peptide and the neurofibrillary degeneration, associated with synaptic alterations, involving mostly the dendritic spines. This study is based on the morphological analysis of 10 brains, 5 of which were obtained from patients who suffered from Alzheimer's disease and 5 from nondemented senile individuals used as control group. The segments taken in major from the occipital lobe were studied with the use of Golgi method, as well as Gallyas' and Bielschowski' s staining methods. In most of the pyramidal cells in the affected brains, there seems to be important spine loss and extensive dendrite pathology. Apical dendrites are distorted and tortuous. Horizontal dendritic arborization is severely decreased leading to an amputated, bell-shaped cell soma. Senile plaques have been often revealed, and neurofibrillary changes have also been noticed.

Unraveling the Possible Routes of SARS-COV-2 Invasion into the Central Nervous System.

PURPOSE OF REVIEW: To describe the possible neuroinvasion pathways of Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2), the virus responsible for the Coronavirus disease-19 (Covid-19) pandemic. RECENT FINDINGS: We present data regarding the family of Coronaviruses (CoVs) and the central nervous system (CNS), and describe parallels between SARS-CoV-2 and other members of the family, which have been investigated in more depth and combine these findings with the recent advancements regarding SARS-CoV-2. SUMMARY: SARS-CoV-2 like other CoVs is neuroinvasive, neurotropic and neurovirulent. Two main pathways of CNS penetration seem to be the strongest candidates, the hematogenous and the neuronal. Τhe olfactory route in particular appears to play a significant role in neuroinvasion of coronaviruses and SARS-CoV-2, as well. However, existing data suggest that other routes, involving the nasal epithelium in general, lymphatic tissue and the CSF may also play roles in SARS-CoV-2 invasion into the CNS.

Purkinje Cells Pathology in Alzheimer's Disease.

Alzheimer's disease (AD) is one of the main causes of dementia in senium and presenium. It is clinically characterized by memory impairment, deterioration of intellectual faculties, and loss of professional skills. The cerebellum is a critical part in the distributed neural circuits participating not only in motor function but also in autonomic, limbic, and cognitive behaviors. In present study, we aim to investigate the morphological changes in the Purkinje cells in different cerebellar regions in AD and to correlate them with the underlying AD pathology. Purkinje cells exhibit significant morphometric alterations in AD and prominently in the anterior lobe which is related to higher cognitive functions. The present study gives new insights into the cerebellar pathology in AD and confirms that Purkinje cells pathology is a key finding in AD brains and that AD is characterized by regional-specific atrophy picked in the anterior cerebellar lobe.

Antibodies against GM1 in demented patients.

The aim of this study was to evaluate the levels of anti-GM1 in demented patients, correlating them with the type and severity of dementia as well as with the eventually coexistent polyneuropathy. Anti-GM1 concentrations were measured in the sera of 33 demented patients with a male-to-female ratio of 1:2.7 (the mean age was 69.7 years for males and 70.1 years for females). Eighty-two percent of the patients revealed increased values of anti-GM1, but only 18.2% demonstrated polyneuropathies. Fifty-nine percent of the patients suffered from vascular dementia. The most severely demented patients demonstrated a Mini-Mental State Examination score of 5 to 23 out of 30 and revealed the most increased levels of anti-GM1 (>40 EU/mL). The findings of this study are indicative of a possible correlation between the levels of anti-GM1 and the severity of dementia, mainly of the vascular type.

Pathological alterations of the climbing fibres of the cerebellum in vascular dementia: a Golgi and electron microscope study.

The climbing fibres originating from the inferior olivary nucleus act as a powerful excitation on the Purkinje cells of the cerebellar cortex that may play a substantial role in the motor performances and the learning of new motor skills. In vascular dementia the existent vascular alterations may induce many hypoxic or ischemic phenomena, among the others, in the olivocerebellar system affecting the climbing fibres in their way to the molecular layer of the cerebellar cortex. In autopsy cases of vascular dementia, the application of silver impregnation technique and electron microscopy revealed a substantial decrease of the number of the climbing fibres in the cortex of the vermis, the flocculus and the cerebellar hemispheres. The presynaptic varicosities and the synaptic terminals of the climbing fibres on the Purkinje cell dendrites were decreased in number and moreover were characterized by a marked poverty of synaptic vesicles. The synaptic cleft was mostly abnormal and wider than 20 nm. Mitochondrial abnormalities, such as elongated mitochondria with disruption of the cristae were seen in the terminal branches of the climbing fibre arborization as well as in the presynaptic components. The blood capillaries demonstrated a considerable thickness of the basal membrane and perivascular astrocytic proliferation, whereas the tight junctions between the endothelial cells were ultrastructurally intact. We would hypothesize that the morphological and morphometric alterations of the climbing fibres of the cerebellar cortex in cases of vascular dementia might be associated with the frequently noticed difficulty in the performance of fine and skilful movements by the patients.

Dendritic and spinal pathology in the acoustic cortex in Alzheimer's disease: morphological and morphometric estimation by Golgi technique and electron microscopy.

CONCLUSIONS: The morphological and morphometric estimation of the dendrites and the dendritic spines in the acoustic cortex in Alzheimer's disease revealed substantial alterations of the dendritic arborization and marked loss of the dendritic spines. This may be related to communication impairment even in early cases of Alzheimer's disease. OBJECTIVES: Alzheimer's disease is characterized by progressive loss of memory, impairment of judgment, and decline in communication and speech eloquence. In the present study we attempted to describe the morphological and morphometric alterations of the dendrites and the dendritic spines in the acoustic cortex in early cases of Alzheimer's disease, in order to approach the communication impairment of patients suffering from Alzheimer's disease, from the neuropathological point of view. MATERIALS AND METHODS: We studied the acoustic cortex in 22 cases of Alzheimer's disease by Golgi technique and electron microscopy. RESULTS: The morphological and morphometric estimation of the acoustic cortex revealed loss of Cajal-Retzius cells in layer I, as well as an impressive abbreviation of the dendritic fields associated with loss of dendritic spines in all layers of the cortex. Numerous distorted, dystrophic and degenerated dendritic spines were also seen, which were intermixed with a considerable number of giant spines. The dendritic and spinal alterations were closely associated with mitochondrial alterations.

Spinal Alterations of Reil Insula in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that involves numerous cellular and biochemical mechanisms resulting in synaptic alterations and extensive neuronal loss. It is primarily characterized by impairment of memory, associated frequently with mood disorders. Continuous studies have shown that insula may be an important target of AD, but neuropathological alterations have not been described extensively. In the present study, we attempted to describe the morphometric and morphological changes of the spines of Reil insula in AD in comparison with normal aging using a silver impregnation technique. We classified spines into 3 types: (1) long neck, (2) short stubby, and (3) other types; and we measured and correlated the length of them in normal controls and in individuals with AD using ImageJ application. Statistical analysis was based on the Student t test on the basis of 360 cells in SPSS v.17.0, and significance was taken as P < .05.

Mitochondrial alterations in Alzheimer's disease.

Morphological alterations of mitochondria may be related to metabolic and energy deficiency in neurons in Alzheimer's disease and other neurodegenerative disorders. Mitochondrial dysfunction is also a hallmark of beta peptide induced neuronal toxicity in Alzheimer's disease. A general change in glucose utilization, increased oxidative stress, and Ca;{2+} deregulation are additional metabolic defects in the AD brain that may also be associated with defective mitochondrial function the result is a cycle of increased mitochondrial dysfunction causing increased oxidative damage until the cellular energy supply falls below the threshold for cellular survival. In a series of studies on the morphological and morphometric estimation of mitochondria in Alzheimer's disease, by electron microscopy we noticed substantial morphological and morphometric changes in the neurons of the hippocampus, the acoustic cortex, the frontal cortex, the cerebellar cortex, the climbing fibers, the thalamus, the globus pallidus, the red nucleus and the locus coeruleus. The morphological alterations consisted of considerable changes of the mitochondrial cristae, accumulation of osmiophilic material, and decrease of their size, in comparison with the normal controls. Mitochondrial alterations were particularly prominent in neurons, which showed loss of dendritic spines and abbreviation of the dendritic arborization. The ultrastructural study of large number of neurons in the thalamus and the red nucleus revealed that the mitochondrial alterations did not coexist with cytoskeletal pathology and accumulation of amyloid deposits, though they were prominent in neurons, which demonstrated fragmentation of the cisternae of the Golgi apparatus. Morphometric analysis showed that mitochondria are significantly reduced in Alzheimer's disease. The relationship between the site and extent of mitochondrial abnormalities and the synaptic alterations suggests an intimate and early association between these features in Alzheimer's disease.

Morphological alterations of the synapses in the locus coeruleus in Parkinson's disease.

Parkinson's disease is the most common movement disorder in the broad spectrum of neurodegenerative diseases, associated frequently with gradual decline of the higher mental faculties. From the morphological point of view it is characterized by the degeneration of a substantial number of dopaminergic neurons of the substantia nigra and a considerable degeneration of neuronal networks in locus coeruleus, putamen, globus pallidus, thalamus and some areas of the cortex of the brain hemispheres. Filamentous inclusions, in the form of Lewy bodies and Lewy neuritis, composed mainly of alpha synuclein, been the hallmark of diffuse Lewy body dementia, have been described in the neurons of the substantia nigra in many cases of Parkinson's disease associated with dementia. In previous studies we have described the morphological alterations in the synapses in the caudate nucleus and the globus pallidus in cases of Parkinson's disease. In the present study we attempted to describe the morphological and morphometric alterations of the locus coeruleus in patients who suffered from Parkinson's disease with normal cognitive function and in patients who suffered from Parkinson's disease associated with dementia, comparing them with normal controls. The morphological alterations of the neurons, the dendrites, the retrograde axonic collaterals and the synapses were more impressive in cases of Parkinson's disease associated with dementia than in Parkinson's disease with normal cognitive function. The majority of the synapses demonstrated changes in size and shape of the pre- and postsynaptic components, polymorphism of the synaptic vesicles and marked morphological alterations of the mitochondria. The morphological alterations of the synapses in cases of Parkinson's disease associated with dementia, plead in favor of the importance of the neuronal circuits of locus coeruleus in cognitive functions.

Mammillary Bodies in Alzheimer's Disease: A Golgi and Electron Microscope Study.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by irreversible memory decline, concerning no rarely spatial memory and orientation, alterations of the mood and personality, gradual loss of motor skills, and substantial loss of capacities obtained by previous long education. We attempted to describe the morphological findings of the mammillary bodies in early cases of AD. Samples were processed for electron microscopy and silver impregnation techniques. The nuclei of the mammillary bodies demonstrated a substantial decrease in the neuronal population and marked abbreviation of dendritic arbors. Decrease in spine density and morphological abnormalities of dendritic spines was also seen. Synaptic alterations were prominent. Alzheimer's pathology, such as deposits of amyloid-ß peptide and neurofibrillary degeneration, was minimal. Electron microscopy revealed mitochondrial alterations and fragmentation of Golgi apparatus, associated frequently with synaptic pathology.

The acoustic cortex in vascular dementia: a Golgi and electron microscope study.

Morphological alterations in vascular dementia have been extensively described in the hippocampus, the cerebral cortex, the subcortical centers and the cerebellum. In the present study, we describe the morphological alterations of the acoustic cortex in five cases, which fulfilled the clinical, neuropsychological and laboratory diagnostic criteria of vascular dementia. The morphological alterations, seen in Golgi technique and electron microscopy concerned the capillaries, the dendritic arborization of the neurons, the astrocytes and the cytoarchitecture of the cortex. The neurons showed an impressive abbreviation of the dendritic fields and loss of spines. Astrocytic proliferation was seen in the cortex. The layer I showed marked decline of Cajal-Retzius cells. The majority of the synapses demonstrated changes in size and shape of the pre- and postsynaptic components and alterations of the organelles. The morphological alterations of the acoustic cortex in vascular dementia may be associated with the impairment of the verbal communication, which is not an uncommon phenomenon even in the early stages of the vascular dementia.

Staining of dead neurons by the Golgi method in autopsy material.

Golgi silver impregnation techniques remain ideal methods for the visualization of the neurons as a whole in formalin fixed brains and paraffin sections, enabling to obtain insight into the morphological and morphometric characters of the dendritic arbor, and the estimation of the morphology of the spines and the spinal density, since they delineate the profile of nerve cells with unique clarity and precision. In addition, the Golgi technique enables the study of the topographic relationships between neurons and neuronal circuits in normal conditions, and the following of the spatiotemporal morphological alterations occurring during degenerative processes. The Golgi technique has undergone many modifications in order to be enhanced and to obtain the optimal and maximal visualization of neurons and neuronal processes, the minimal precipitations, the abbreviation of the time required for the procedure, enabling the accurate study and description of specific structures of the brain. In the visualization of the sequential stages of the neuronal degeneration and death, the Golgi method plays a prominent role in the visualization of degenerating axons and dendrites, synaptic "boutons," and axonal terminals and organelles of the cell body. In addition, new versions of the techniques increases the capacity of precise observation of the neurofibrillary degeneration, the proliferation of astrocytes, the activation of the microglia, and the morphology of capillaries in autopsy material of debilitating diseases of the central nervous system.

The hypothalamus in Alzheimer's disease: a Golgi and electron microscope study.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by irreversible decline of mental faculties, emotional and behavioral changes, loss of motor skills, and dysfunction of autonomic nervous system and disruption of circadian rhythms (CRs). We attempted to describe the morphological findings of the hypothalamus in early cases of AD, focusing our study mostly on the suprachiasmatic nucleus (SCN), the supraoptic nucleus (SON), and the paraventricular nucleus (PVN). Samples were processed for electron microscopy and silver impregnation techniques. The hypothalamic nuclei demonstrated a substantial decrease in the neuronal population, which was particularly prominent in the SCN. Marked abbreviation of dendritic arborization, in association with spinal pathology, was also seen. The SON and PVN demonstrated a substantial number of dystrophic axons and abnormal spines. Alzheimer's pathology, such as deposits of amyloid-ß peptide and neurofibrillary degeneration, was minimal. Electron microscopy revealed mitochondrial alterations in the cell body and the dendritic branches. The morphological alterations of the hypothalamic nuclei in early cases of AD may be related to the gradual alteration of CRs and the instability of autonomic regulation.

Age-related dendritic and spinal alterations of pyramidal cells of the human visual cortex.

INTRODUCTION: Normal aging is characterized by deterioration of visual abilities, affecting mainly visual acuity, contrast and wavelength sensitivity. In the present study we attempted to describe the morphological and morphometric alterations of the dendrites and the dendritic spines of the pyramidal cells of the visual cortex during normal aging, in order to approach the visual impairment of aged individuals from a neuropathological point of view. MATERIAL AND METHODS: We studied the visual cortex in 20 brains using the Golgi technique. RESULTS: In pyramidal cells, which represent the majority of cortical neurons, age-related pathology can be observed in cell somata as well as, most importantly, in dendrite number and morphology. The apical dendrites of some pyramidal cells are distorted and tortuous. Horizontal dendritic arborization is also severely decreased. These alterations were more prominent in the corticocortical pyramidal neurons of the 5th layer. CONCLUSIONS: The morphological and morphometric assessment of the dendrites and the dendritic spines in the visual cortex in normal aging revealed substantial alterations of the dendritic arborization and marked loss of the dendritic spines, which may be related to visual impairment even in normal aging.

Mitochondrial alterations in Alzheimer's disease.

Morphological alterations of mitochondria may be related to metabolic and energy deficiency in neurons in Alzheimer's disease (AD) and other neurodegenerative disorders. In previous studies on the morphological and morphometric estimation of mitochondria in AD electron microscopy revealed substantial morphological and morphometric changes in the hippocampus, the acoustic cortex, the frontal cortex, and the cerebellum. This study extends this observation to subcortical centers, namely the thalamus, the globus pallidus, the red nucleus, and the locus caeruleus in 10 brains of patients who suffered from AD. The morphological alterations consisted of very obvious changes of the mitochondrial cristae, accumulation of osmiophilic material and decrease of their size, in comparison with the normal controls. Mitochondrial alterations were particularly prominent in neurons, which showed loss of dendritic spines and abbreviation of the dendritic arborization. The ultrastructural study of a large number of neurons in the thalamus and the red nucleus revealed that the mitochondrial alterations did not coexist with cytoskeletal pathology and accumulation of amyloid deposits. However, they were prominent in neurons, which demonstrated fragmentation of the cisternae of the Golgi apparatus. The morphological alterations of the mitochondria presumably suggest oxidative damage in neurons in AD brains.