Reduced in vitro phosphorylation of synapsin I (site 1) in Alzheimer's disease postmortem tissues.

Homogenates prepared from the temporal cortex and hippocampus of individuals who had histopathologically confirmed Alzheimer's disease exhibited reduced in vitro cyclic AMP-dependent phosphorylation of synapsin I, neuronal phosphoprotein. One specific phosphorylation site (site 1) was affected while two other sites, which are phosphorylated by calcium/calmodulin kinase II, exhibited no such differences. Other phosphoproteins such as pyruvate dehydrogenase, did not show these differences.

Aluminum, Alzheimer's disease, and the olfactory system.

In Alzheimer's disease, it has been recognized that there is a dramatic tendency for the development of neurofibrillary tangles among neurons of cortical regions associated with the olfactory system. We have demonstrated that neurofibrillary tangle-bearing neurons contain dramatically elevated levels of aluminum. The olfactory system, the only portion of the central nervous system with exposure to the external environment, is uniquely capable of uptake and transneuronal spread of exogenous substances.

Two decades of increasing mortality from Parkinson's disease among the US elderly.

To examine the possible role of environmental factors in the cause of Parkinson's disease (PD), we reviewed mortality trends for PD in the United States from 1962 through 1984. We found that age-specific mortality for PD in all demographic groups had changed notably during this 23-year interval. Among whites of both sexes, substantial declines were observed among the middle-aged, while notable increases were seen in the geriatric age groups.

Microprobe studies of aluminum accumulation in association with human central nervous system disease.

The neurofibrillary tangle, first described by Alzheimer in 1907, along with the senile plaque, represent the two principle neuropathologic lesions identified in the brains of patients with Alzheimer's disease. Aluminum salts inoculated into the central nervous system of certain experimental animals induces neurofilamentous lesions which are similar, but not identical to the neurofibrillary tangles seen in Alzheimer's disease. Although some reports provide evidence of increased amounts of aluminum in the brains of Alzheimer's disease victims, such bulk analysis studies have been difficult to replicate.

Parkinsonism death rates by race, sex and geography: a 1980s update.

To evaluate temporal changes in the geographic distribution of Parkinson's disease (PD) mortality in the United States, we reviewed death rates for PD in the nine regions of the United States for 1980-1984. Age-adjusted mortality for all ages and for the elderly (65 years of age and older) was analyzed. Variation in PD mortality was observed among the regions for all demographic groups.

Differential brain expression of the Alzheimer's amyloid precursor protein.

The expression of the Alzheimer amyloid protein precursor (AAPP) was examined in human, monkey, dog and rat brains. Two proteins, one identified as AAPP695 and the other as AAPP751, were immunoprecipitated from the in vitro translation of human, dog and rat brain polysomes. The AAPP751 to AAPP695 ratio was highest in human, intermediate in dog and lowest in rat brain polysomes.

Genetics and Alzheimer's disease: notes of an environment watcher (with apologies to L. Thomas).

Support has recently been voiced for the genetic hypothesis of Alzheimer's disease; frequently at the expense of considerations of environmental factors. In the adult, genetic diseases rarely exist without modification by environment forces. Atherosclerosis leading to myocardial infarction may provide a useful model to consider genetic and environmental factors in Alzheimer's disease.

Multiple microabscesses in the central nervous system: a clinicopathologic study.

We reviewed 2,107 consecutive autopsies with neuropathologic examination at the Medical Center Hospital of Vermont, and identified 92 cases with significant pathologic evidence for infection involving the central nervous system (CNS). Of these, 35 took the form of multiple microabscesses. There were 19 men and 16 women, mean age 56.

Rising mortality from motoneuron disease in the USA, 1962-84.

From 1962 to 1984, age-specific mortality for motoneuron disease (MND) in the United States rose in all demographic groups over the age of 40. The increase was seen in both men and women, and both whites and non-whites, and was most pronounced in the elderly (eg, 378% in white women aged 80-84 years). Men were at 50% higher risk than women, and whites had twice the risk of non-whites.

Aluminum-induced neurofibrillary degeneration affects a subset of neurons in rabbit cerebral cortex, basal forebrain and upper brainstem.

Neurofibrillary tangles in Alzheimer's disease show a predilection for cortical pyramidal and subcortical projection neurons. The antigenic composition, neuronal specificity and distribution of aluminum-induced neurofibrillary degeneration were examined in regions of rabbit brain analogous to those that develop neurofibrillary tangles in Alzheimer's disease. Neurofibrillary degeneration was induced by intraventricular instillation of aluminum chloride.

Aluminum-induced neurofibrillary degeneration disrupts acquisition of the rabbit's classically conditioned nictitating membrane response.

Rabbits received intraventricular injections of aluminum chloride, hydrochloric acid, or served as unoperated controls. On the 6th day postsurgery, they underwent 4 days (100 trials per day) of classical conditioning of the nictitating membrane response (NMR) to a tone conditioned stimulus and an air-puff unconditioned stimulus. Unoperated and hydrochloric acid control animals readily acquired the conditioned response.

Accumulation of phosphorylated neurofilaments in anterior horn motoneurons of amyotrophic lateral sclerosis patients.

Perikaryal collections of intermediate filaments have been described in the anterior horn motoneurons of patients with amyotrophic lateral sclerosis (ALS), but these inclusions have generally been considered rare and mainly associated with the familial form of ALS. Using the monoclonal antibody NF2F11, which recognizes phosphorylated neurofilament epitopes, we showed that focal collections of neurofilaments in anterior horn motoneurons were a characteristic finding in sporadic as well as in familial ALS; they were present in seven of nine ALS patients, but in none of nine control spinal cords. These neurofilamentous collections are not cross-reactive with antibodies directed against paired helical filaments and the microtubule associated protein tau.

Disrupted retention of the classically conditioned nictitating membrane response in rabbits with aluminum-induced neurofibrillary degeneration.

Rabbits underwent classical conditioning of the nictitating membrane response (NMR) to a tone conditioned stimulus and an air puff unconditioned stimulus until they emitted 90 percent or greater conditioned responses (CRs) for two consecutive days. They then received intraventricular injection of aluminum chloride, hydrochloric acid or saline. Ten days post injection they were tested for retention of the conditioned response.

Adult onset Hallervorden-Spatz disease with neurofibrillary pathology. A discrete clinicopathological entity.

Three adults with progressive cognitive decline and extrapyramidal dysfunction were studied. They were all mentally retarded women without known chromosomal abnormalities, ranging in age at the time of onset from 31 to 42 yrs with an average duration of illness of 6 yrs. Neurological signs were stereotyped and consisted of a unilateral equinovarus foot posture followed by progressive dementia, rigidity and quadriparesis.

Comparison of cytomegalovirus infection of brain and lung in a patient with subacute encephalopathy of acquired immunodeficiency syndrome.

The ultrastructure of cytomegalovirus infection of glial cells in an area of demyelination in the brain of a patient with subacute encephalopathy associated with acquired immunodeficiency syndrome is described. By comparison with the lung of the same patient, the cytomegalovirus-infected brain showed a lower density of complete virions per cell and a higher proportion of defective viral particles.

The association of aluminum Alzheimer's disease, and neurofibrillary tangles.

Alzheimer's disease is a progressive neurodegenerative disease characterized by the development of large numbers of neurofibrillary tangles in certain neuronal populations. Aluminum salts inoculated into experimental animals produce neurofilamentous lesions which are similar, but not identical, to the neurofibrillary tangle of Alzheimer's disease. Although a few reports suggest evidence of increased amounts of aluminum in the brains of Alzheimer's disease victims, such bulk analysis studies have been difficult to replicate.

Aluminum neurotoxicity--potential role in the pathogenesis of neurofibrillary tangle formation.

Alzheimer's disease is a progressive neurodegenerative disease characterized neuropathologically by the development of large numbers of neurofibrillary tangles in certain neuronal populations of affected brains. This paper presents a review of the available evidence which suggests that aluminum is associated with Alzheimer's disease and specifically with the development of the neurofibrillary tangle. Aluminum salts inoculated into experimental animals produce neurofilamentous lesions which are similar, though not identical, to the neurofibrillary tangle of man.

Familial myoclonic dementia masquerading as Creutzfeldt-Jakob disease.

We describe a kindred with 7 confirmed and 2 probable cases of subacute dementia accompanied by myoclonus. The inheritance pattern is consistent with autosomal dominance and shows anticipation. The pathological changes involve marked gliosis with neuronal loss of the dorsomedial and midline thalamic nuclei, with lesser involvement of the anterior, lateral, and posterior thalamic nuclei.

Neuropathology of dementia.

This article summarizes the neuropathologic changes seen in several of the more common disorders that lead to dementia. The most important, Alzheimer's disease, is characterized by the widespread development of neurofibrillary tangles and senile or neuritic plaques in the hippocampus and neocortex. Another important underlying cause of dementia is multiple infarction (so-called multi-infarct dementia), in the form of numerous cortical lesions, multiple basal ganglia lacunar infarcts, or multiple white matter infarctions.

An immunocytochemical comparison of cytoskeletal proteins in aluminum-induced and Alzheimer-type neurofibrillary tangles.

Exposure of the central nervous system (CNS) of rabbits to aluminum salts produces a progressive encephalopathy. Examination of CNS structures discloses widespread perikaryal neurofibrillary tangle (NFTs) formation. The aluminum-induced NFTs consist of collections of normal neurofilaments, and differ ultrastructurally and in their solubility characteristics from Alzheimer-type NFTs, the latter being composed of largely insoluble paired helical filaments.

Relationship of aluminum to Alzheimer's disease.

Alzheimer's disease is a progressive degenerative brain disease of unknown etiology, characterized by the development of large numbers of neurofibrillary tangles and senile plaques in the brain. Aluminum salts may be used experimentally to produce lesions which are similar, but not identical, to the neurofibrillary tangle. Although some studies have reported increased amounts of aluminum in the brains of Alzheimer's disease victims, these bulk analysis studies have been difficult to replicate and remain controversial.