Journal of Alzheimer's Disease - Volume 1, issue 2

Authors: Dowson, J.H. | Mountjoy, C.Q. | Cairns, M.R. | Wilton-Cox, H. | Bondareff, W.

Article Type: Research Article

Abstract: Cerebellar tissue was examined from 22 patients with Alzheimer's disease (AD) and from an age-matched group of 20 non-diseased subjects. Intraneuronal lipopigment in the bodies of 1344 Purkinje cells (PCs) (32 per brain) was identified by fluorescence microscopy. The mean total area (per PC) of the outlines of discrete regions of lipopigment in a PC perikaryon for the AD-related group of PCs was significantly greater than the mean for the comparison group (p < 0.001). Also, the two groups of PCs showed significant (< 0.05) differences in the mean number (per PC) of discrete regions of lipopigment in 11 size categories. The findings …indicate a lysosomal abnormality in PCs in AD. The pattern of size distribution of lipopigment in PCs differed from that previously-reported for neurons of the frontal cortex. These differences may be associated with the absence of senile plaques and the presence of “diffuse” amyloid plaques in the cerebellum in AD Show more

Keywords: Alzheimer's disease , aging, lipopigment, lipofuscin, Purkinje cells, cerebellum

DOI: 10.3233/JAD-1998-1201

Citation: Journal of Alzheimer's Disease, vol. 1, no. 2, pp. 71-79, 1998

Authors: Kazee, Ann M. | Johnson, Eileen M.

Article Type: Research Article

Abstract: The purpose of this study was to quantitate the extent of neuropathological lesions (neurofilbrillary tangles and senile plaques) characteristic of Alzheimer's disease in cognitively intact elderly control subjects. The subjects included twenty-six elderly individuals who were autopsied at a university-based Alzheimer's Disease Center. The mean age at autopsy was 78 years (range 51–99 years); there were 15 males and 11 females. All of these control subjects had a few neurons containing neurofibrillary tangles in the hippocampus, but no neurofibrillary tangles in the neocortex. Twelve of the 26 subjects (46%) had some senile plaques in the neocortex, while fourteen (54%) did …not. Six subjects (23%) had substantial numbers of senile plaques in the neocortex. Neither the number of neurons containing neurofibrillary tangles nor the number of senile plaques correlated with age in these subjects. Possible conclusions are that there are many elderly individuals with incipient Alzheimer's Disease, or that one can have some degree of these lesions and still be cognitively normal. These data point out the need to have better pathological markers of the disease process and better diagnostic criteria to define Alzheimer's Disease. Show more

DOI: 10.3233/JAD-1998-1202

Citation: Journal of Alzheimer's Disease, vol. 1, no. 2, pp. 81-89, 1998

Authors: Bissette, Garth | Cook, Larry | Smith, Wayne | Dole, Kenneth C. | Crain, Barbara | Nemeroff, Charles B.

Article Type: Research Article

Abstract: Background: the neuropeptides most consistently reported to be altered in Alzheimer’s disease are corticotropin-releasing factor and somatostatin (somatotropin-release inhibiting factor), although this has been previously assessed in a limited number of brain regions. Methods: in order to comprehensively characterize the involvement of these two anatomically distinct neuropeptide systems in Alzheimer’s disease and to determine if they are equally involved in the associated pathology, we measured the concentration of corticotropin-releasing factor and somatostatin in post-mortem brain tissue. Radioimmunoassay of 24 cortical and 13 sub-cortical brain regions from 16 cases of neuropathologically confirmed AD and 9 non-Alzheimer’s disease controls were …performed and significant differences in group regional neuropeptide concentrations were sought using the Student Newman-Keuls test after ANOVA. Results: comparison of group mean regional neuropeptide concentrations revealed several brain regions where both peptides were decreased in Alzheimer’s disease and some regions where only one of the two peptides were decreased, while still other regions exhibited no changes in either peptide. These changes were principally found in frontal and temporal cortex, with few subcortical regions exhibiting pathologic changes in peptide concentration. Regional peptide content was correlated among peptides and with duration of dementia in several brain regions. Conclusions: these data support the hypothesis that the somatostatin- and corticotropin-releasing factor containing neurons are pathologically involved in AD and that the involved neurons are limited to specific areas of the brain. Show more

DOI: 10.3233/JAD-1998-1203

Citation: Journal of Alzheimer's Disease, vol. 1, no. 2, pp. 91-105, 1998

Authors: Salehi, A. | Pool, C.W. | Mulder, M. | Ravid, R. | Gonatas, N.K. | Swaab, D.F.

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is neuropathologically characterized by neuritic plaques (NPs) and neurofibrillary tangles and functionally by a decreased metabolic rate of neurons. Our previous studies showed that in brain areas which are extensively affected by plaques and tangles, i.e. the CA1 area of the hippocampus and the hypothalamic tuberomamillary nucleus, neuronal protein synthetic ability is significantly lower in AD patients than in controls. However, the presence of tangles as shown by Bodian staining appeared not to be directly related to decreased protein synthetic ability of neurons. In order to study to what extent the metabolic function of neurons might be …affected by the other neuropathological hallmark of AD, i.e. NPs, which are presumed to contain neurotoxic compounds, we studied eight severely demented AD patients matched for the ApoE genotype (ApoE 3/3). Using an image analysis system, the size of the neuronal Golgi apparatus (GA) and of the cell profile area was measured as a parameter for protein synthetic activity in the CA1 area of these patients. NPs were stained by Bodian, and subsequently the distance of each neuron with an immunostained GA to the nearest NP was measured. Our results showed that neither NP density nor the distance between NPs and neurons correlated with the protein synthetic ability of neurons as judged by the size of the GA. Based on these results we suggest that in AD the presence of NPs and decreased neuronal protein synthetic ability are basically two independent phenomena Show more

Keywords: Alzheimer, CA1 area, neuritic plaque, hippocampus, ApoE, Golgi apparatus

DOI: 10.3233/JAD-1998-1204

Citation: Journal of Alzheimer's Disease, vol. 1, no. 2, pp. 107-118, 1998

Authors: Etiene, Dannie | Kraft, Joanny | Ganju, Neema | Gomez-Isla, Teresa | Gemelli, Brad | Hyman, Bradley T. | Hedley-Whyte, E. Tessa | Wands, Jack R. | de la Monte, Suzanne M.

Article Type: Research Article

Abstract: Heterogeneous pathology in Alzheimer's Disease (AD) is due to variability in the nature and severity of lesions, overlap with other neurodegenerative diseases such as Parkinson's disease, or the co-existence of cerebrovascular disease. In the MGH-ADRC autopsy archives, remote cerebral infarcts (CVA) were reported in 30% of the otherwise uncomplicated AD cases. To determine the potential significance of cerebrovascular lesions in relation to AD, the relative densities (CERAD grading criteria) of Bielschowsky-stained AD lesions and Ab-amyloid immunoreactive plaques were compared among cases of AD+CVA (N = 52), AD (N = 48), aged controls (NC; N = 9), and aged controls with AD lesions (ADC; N = 8). The prevalence …of the ApoE e4 allele was also determined for each group. This study demonstrated: 1) higher densities of Bielschowsky-stained plaques in AD, AD+CVA, and ADC than in NC (P < 0.0001); 2) more abundant neurofibrillary tangles in AD relative to all other groups (P < 0.0005), and in AD+CVA and ADC relative to NC (P < 0.05); and 3) increased densities of Aβ-amyloid-immunoreactive plaques in AD relative to AD+CVA (P = 0.0003). In AD+CVA, cerebral vascular lesions consisting of remote microscopic cortical and subcortical white matter infarcts, ischemic lesions, and leukoaraiosis were consistently distributed in structures typically damaged by AD neurodegeneration, as well as in the basal ganglia. The ApoE ε4 allele was more prevalent in the AD+CVA (70%) than in the AD (58%) group (P = 0.05). Since the AD and AD+CVA groups had similar degrees of dementia, the results suggest that cerebral vascular lesions in regions typically destroyed by AD may contribute to the clinical manifestations of AD. Show more

Keywords: Alzheimer's disease, cerebral infarction, multi-infarct dementia, Aβ-amyloid, Apolipoprotein E

DOI: 10.3233/JAD-1998-1205

Citation: Journal of Alzheimer's Disease, vol. 1, no. 2, pp. 119-134, 1998