12. A quantitative morphological study of changes in human cerebral cortex in normal aging and senile dementia of the Alzheimer type (SDAT)

C.A.J. Broere, A. Keyser, R. Nieuwenhuys and B.P.M. Schulte (Nijmegen, The Netherlands)

Changes in cortical neuron number during normal aging are reported. However, the literature concerning the extent of neu- ronal cell loss is conflicting. There is no agreement on the distribution of cortical cell loss either. The occur- rence of cortical pathology in SDAT has been thought by some authors (see for review Perry et al., Brit. Med. Bull. 1986, 42:63) to be a consequence of pri- mary pathological changes (e.g., neurofibrillary tang- les (NFT), senile plaques (SP), granulovacuolor de- generation (GD), satelitosis (S) and gliosis (G)) in the hippocampus and subcortical nuclei (e.g., nucleus basalis (Meynert) (nBM), locus coerulues (LC), nu-

cleus raphe dorsalis (NRD)). The changes in the neo- cortex are considered to be primary by other authors. Morrison et al. (in: Scheibel et al., Biological substra- tes of Alzheimer's disease, 1986) regard SDAT as a "Global Neocortical Disconnection Syndrome" (GNDS). This view is based on cortical SP distribu- tions and SP morphology: SP are most prevalent in neurons of cortical layers, characterized by large py- ramidal cells (source neurons for cortical projection). In this study the distribution of neurons, NFT and SP versus cortical depth is investigated. Cortical areas with the largest deviation from normal will be identi- fied by a photodensitometer method. These areas will be subjected to a detailed analysis using an unbiased stereological method.

13. Deficient repair capability in Alzheimer's disease

Herman S. Bachelard and Ann P. Walker (London, UK)

The following activities of ADP-ribose transferase, an enzyme involved with DNA ligase in repairing damage to DNA, have been observed. In A, the temporal lobe samples were taken 1l/2-2 days post- mortem and the delay for the Alzheimer's samples was not significantly different from control. Diagnosis was based on morphology; enzyme activi- ties are significantly different from control. In B the

A. Nuclei Alzheimer neuronal control neuronal Alzheimer glial control glial B. Alzheimer neuronal control neuronal Alzheimer glial control glial

Age (yr) 90 ± 7 90 ± 4 95 ± 3 92 ± 2

post-mortem delay was very small (11/2-2 hr), the sam- ples were from parietal lobe and the activities are generally higher than in A. Though the mean values of B of the Alzheimer's samples (ca 9000) are much lower than control (ca 20000) the results are not signi- ficant; one Alzheimer sample gave a very high result. Further samples are being analysed. Values are cpm/min/106 nuclei - S.D. ; *P<0.01 (un- paired t test); # one control sample showed extensive gliosis.

PMdelay (hr) n Activity 43 ± 10 6 2380 ± 1390" 34 ± 13 7 6640 ± 5120 40 ± 7 3 2510 ± 2040* 3 0 ± 2 4 7970± 2280

5 9400 + 8900 4 20100 + 9100 5 8600 + 9100 4 23500 + 21100#

14. Neuropathological heterogeneity within a family with dominantly inherited Alzheimer's disease

Peter Frommelt, Rail Schnabel, Friedemann Manz, Linda E. Nee and Ronald J. Polinsky (Lemgo and Bielefeld, FRG; Bethesda MD, USA)

We report on a Western German family with autoso- mal dominant Alzheimer's disease (AD), affecting 19 members in 5 generations. Down's syndrome does not occur. AD starts between 39 and 56 (average 49) years. Duration varies between 2 and 13 (average 6) years. The clinical course is rather similar: starting with memory disturbances and loss of interest, apha-

sia and agraphia follow, later on beside progressive cognitive decline some hypokinesia and rigor occur and in the final stage there are myoclonus and epilep- tic seizures. There are no cerebellar signs. EEG (n=8) revealed diffuse slowing. CT-scan (n=5) and nuclear magnetic resonance imaging (n=2) sho- wed diffuse cortical atrophy without cerebellar patho- logy. An overall reduction in cerebral glucose meta- bolism most severe in the parietal and temporal areas was demonstrated by positron emission tomography (n=2).

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