The distribution of astrocytic gliosis in Alzheimer's disease (AD) and aging cerebrum, as marked by immunoperoxidase staining for glial fibrillary acidic protein (GFAP), was examined in whole-hemisphere coronal sections. Cortical gliosis in AD had an obvious laminar pattern. There were two heavy bands of staining, one in layers II-III and another in layer V. Normal aging cases sometimes displayed considerable cortical gliosis, but no specific patterns were apparent. Most AD cases, and some normal aging cases, displayed hypertrophy of immunoreactive astrocytes at grey matter-white matter interfaces, especially the cortico-medullary junction. Subcortical grey matter gliosis was common in both normal aging and AD, but there was no consistent pattern in either group. The deep cerebral white matter, which is stained evenly and heavily in young, healthy individuals, showed uneven staining in both normal elderly and AD brains. In both AD and aging, perivascular gliosis was prominent throughout the cerebrum and especially in the putamen. In conclusion, both AD and aging cerebri show extensive gliosis: AD cortical gliosis has a specific laminar pattern, but there does not appear to be an AD-specific pattern of subcortical gliosis.

All giant neurons of the medial basal forebrain stained for choline acetyltransferase (ChAT). Cell numbers declined from 400,000 to 475,000 in young controls to approximately 140,000 in elderly controls. Five senile dementia cases had counts ranging from 45,000 to 100,000 cells. ChAT levels in control frontal cortex decreased from 1.2 mumol/hr/100 mg protein at age 40 to 0.5 at age 95. Five senile dementia cases had levels ranging from 0.04 to 0.30. When the cholinergic cell count in the basal forebrain drops below about 100,000 cells, the level of cortical ChAT may be so low that clinical dementia appears.

Cholinergic afferents to the amygdala from the basal forebrain were studied using di-isopropyl fluorophosphate-AChE histochemistry in combination with retrograde tracing using various fluorescent dyes. Cells sending their axons to the amygdala and staining intensely for AChE were located mainly in the nucleus of the substantia innominata. They also were found in the ventral part of the globus pallidus, the horizontal limb of the nucleus tractus diagonalis Broca, and the nucleus interstitialis ansae lenticularis. A correspondence was established between these cells and cells staining for choline acetyltransferase by immunohistochemistry in both distribution and morphology. Non-cholinergic neurons which send their axons to the amygdala also were found in the substantia innominata complex.

We detected crossed cerebellar as well as uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease by positron emission tomography (PET) using 18F-fluorodeoxyglucose. We studied a series of 26 consecutive, clinically diagnosed Alzheimer cases, including 6 proven by later autopsy, and compared them with 9 age-matched controls. We calculated asymmetry indices (AIs) of cerebral metabolic rate for matched left-right regions of interest (ROIs) and determined the extent of diaschisis by correlative analyses. For the Alzheimer group, we found cerebellar AIs correlated negatively, and thalamic AIs positively, with those of the cerebral hemisphere and frontal, temporal, parietal, and angular cortices, while basal ganglia AIs correlated positively with frontal cortical AIs. The only significant correlation of AIs for normal subjects was between the thalamus and cerebral hemisphere. These data indicate that PET is a sensitive technique for detecting diaschisis.

No abstract