Non-serotonergic profiles of lobar atrophies.

Initial studies of dementia due to lobar atrophy (Pick's disease and Dementia of the Frontal Lobe Type, DFT) indicate neurochemical profiles distinct from that of Alzheimer's disease (AD) [1,2]. We have examined the cortical serotonergic profile of previously frozen human brains from control patients (n=27, 178: 1 O? , age 68 f 10 yrs, postmortem delay (PMD) 30 f 20 hrs, mean f s.d.) and patients suffering from histologically confirmed Pick's disease (n=10, 28:8?, age 66 f 6 yrs, PMD 35 f 31 hrs) and DFT (n=6, 38:3?, age 65 f 7 yrs, PMD 41 f 27 hrs). Receptor ligand binding experiments were performed on crude homogenates of frontal (Brodmann Area, BA 9), temporal (BA 21) and parietal (BA 7) cortical areas. Choline acetyl transferase (Chat) activity was determined by a modified method of Fonnum [3]. InM 3H pirenzipine, displaced with 0.1 pM pirenzipine was used to investigate Muscarinic, M, receptors. L and N type Ca" channels were quantified using InM 3H PN 200-110 (displaced with 10pM nicarpidine) and 50pM ' 2 5 1 ~ ~ ~ n ~ t o ~ i n (displaced with 1 pM o-conotoxin) respectively. GABA, binding was determined with 2nM %TBPS (Butyl bicyclophosphonothionate), displaced with 4.75pM TBPS. The glutamate receptors were also investigated: NMDA (5nM 3H dizocilpine displaced with IOpM dizocilpine), AMPA (2nM 3H CNQX (6-cyano-7nitroquinoxaline-2,3-dione) displaced with 0.7mM glutamate) and kainate (2.5nM 3H kainate displaced with 100pM kainate). Somatostatin-like immunoreactivity (SLIR) was determined using a comercially available RIA kit (Incstar). Table 1 shows the neurochemical profiles of the control subjects, and Figure 1 indicates the neurochemical parameters in the disease states as a percentage of these. Classically in AD, ChAT activity is significantly reduced in Alzheimer's disease, in both Pick's disease and DFT the activity of this enzyme is unaffected. 1w