Carolyn M. Coyne

Increased incidence of neurofibrillary tangles (NFT) in non-demented individuals with hypertension.

The incidence rates and numerical densities of argryophilic neurofibrillary tangles (NFT) and senile plaques (SP) were determined in non-demented individuals and subjects with Alzheimers disease (AD). The non-AD subjects were grouped according to cardiac status; those individuals with critical coronary artery disease (cCAD), those hypertensive individuals without cCAD (HyperT), and those without heart disease (non-HD). The incidence and densities of SP and NFT were significantly greater in AD than any of the non-demented groups. The prevalence of SP was increased in both HyperT and cCAD compared to non-HD controls, while NFT occurrence was accentuated in non-demented HyperT subjects only. The densities of SP and NFT in HyperT were elevated compared to cCAD or both cCAD and non-HD controls; NFT densities were similar in cCAD and non-HD. NFT density increased with increasing age in only the non-HD and cCAD groups, suggesting a possible relationship between disease process and NFT formation in the AD and HyperT populations.

Temporal Sequence of Plaque Formation in the Cerebral Cortex of Non-Demented Individuals

One of the hallmarks of Alzheimers disease is the presence of argyrophilic plaques (arg-P) accompanying dementia and other forms of cognitive alterations. In the present investigation 195 non-demented, cognitively normal patients were grouped according to the presence or absence of critical coronary artery disease (cCAD), defined as a 75% or greater stenosis of one of the epicardial arteries. None of the subjects had significant cerebral vascular disease. The parahippocampal gyrus (PHG) and frontal pole were analyzed for the presence of arg-P, A4 deposition, ALZ-50 immunoreactive (IR) neurons and neuropil threads (NT). Individuals with cCAD have a significantly greater incidence of plaques than non-heart disease (non- HD) subjects. Every cCAD subject had ALZ-50 IR neurons in the PHG and a greater incidence of NT as compared to the non-HD subjects. Every subject with plaques also had IR neurons and NT in the PHG. Based on the presumption that early neurodegeneration labeled by ALZ-50 antibody and amyloid deposition are in some way linked, then the sequence of plaque formation is initiated by the presence of ALZ-50 IR neurons followed in order by NT, A4 deposition and diffuse form arg-P.

Increased density of senile plaques (SP), but not neurofibrillary tangles (NFT), in non-demented individuals with the apolipoprotein E4 allele: comparison to confirmed Alzheimer's disease patients

The apolipoprotein E genotype and cortical senile plaque (SP) and cortical and hippocampal neurofibrillary tangle (NFT) densities were determined in non-demented individuals and neuropathologically confirmed AD patients. The non-demented population was further subdivided according to presence or absence of pathologically established critical coronary artery disease (cCAD), hypertension (HyperT), or neither (non-heart disease; non-HD). The apolipoprotein E4 (APOE4) allele incidence and dose frequencies were increased in the AD, cCAD and HyperT groups compared to the non-HD controls. The mean number of SP and NFT was significantly increased with the presence of the APOE4 allele within the entire population. After grouping the non-demented subjects according to cardiac status, SP but not NFT density was increased among those individuals with the APOE4 genotype. In HyperT, the increased density of SP also correlated to the APOE4 allele dose frequency. The density of SP and NFT was increased in all regions of AD brain compared to all other non-demented groups, but no significant difference was found between AD patients with or without an APOE4 allele. These two AD groups were age-matched, but could not be matched for disease duration. The data suggest a relationship between heart disease, APOE4 genotype and the presence of SP regardless of cognitive status.

Oxidative Stress in Sudden Infant Death Syndrome

We investigated the hippocampus and parahippocampal cortex of victims of sudden infant death syndrome and of age-matched infants dying acutely of known causes (non-sudden infant death syndrome controls). Tissue sections were investigated for the presence of neurons expressing signs of elevated levels of free radical using immunohistochemical markers for superoxide dismutase and glutathione peroxidase. Brain tissues displayed immunopositive neurons in every infant. In control infants, an age-related decline in the number of superoxide dismutase- and glutathione peroxidase-immunoreactive neurons was apparent in the hippocampus and parahippocampal cortex. Significantly increased numbers of immunoreactive neurons were found in victims of sudden infant death syndrome under 6 months of age compared to age-matched controls. This suggests that infants who later become victims of sudden infant death syndrome may experience antemortem periods of oxidative stress, elevated levels of free radicals, and compensatory up-regulation of the free radical scavenger enzymes superoxide dismutase and glutathione peroxidase. (J Child Neurol 1996; 11:433-438).

Neurochemical and histopathologic alterations characteristic of Pick's disease in a non-demented individual.

In the course of investigating a large number of non-demented subjects, a 68 year old female dying of coronary artery disease was found to have Pick bodies in her grossly normal brain. Although only mild subcortical gliosis and no neuron loss were observed, Pick bodies were found throughout the brain and occasional balloon cells were noted. Pick bodies and numerous neurons were also ALZ-50 and Tau-1 immunoreactive. Retrospective studies indicated a lack of overt intellectual decline or depression in this individual. Frontal, temporal and occipital poles, amygdala, hypothalamus and nucleus basalis of Meynert (nbM) were analyzed for ChAT, AChE and MAO-A and -B enzymatic activities and for the binding of 5HT and imipramine. Cholinergic decreases were found only in subcortical structures. Serotonin binding decreases were widespread, excluding the nbM. Altered MAO-B activity was regionally variable, and no differences in MAO-A activity or imipramine binding were observed. Few differences in neurochemical alterations were observed in the current non-demented subject with abundant Pick bodies compared to previous studies of demented Picks patients. This case strongly suggests that chemical dysfunction and neuropathological features of Picks disease occur in advance of overt clinical manifestations of the disorder

Recommended Technique for Brain Removal to Retain Anatomic Integrity of the Pineal Gland in Order to Determine Its Size in Sudden Infant Death Syndrome

A standardized removal and dissection procedure is presented for human infant brain. A previously unreported cistern of the pineal gland must be severed at autopsy in order to preserve the glands anatomic integrity during brain removal. Utilization of these methods to investigate Sudden Infant Death Syndrome brain tissue should facilitate interdisciplinary studies and comparisons of inter agency findings. We use these dissection procedures to extend our findings on reduced pineal gland size as an anatomic marker assisting the forensic pathologist in making the diagnosis of Sudden Infant Death Syndrome.