136 Franz J. Kallmann 



This finding and the absence of both senile plaques and neuro- 

 fibrillary changes are usually sufficient to differentiate Pick's 

 from Alzheimer's disease. In fact, the degenerative processes 

 in Pick's disease are so peculiar that, genetically, they would 

 seem to point to a very specific metabolic disorder which has 

 yet to be identified. 



For this purpose, broad interdisciplinary family investiga- 

 tions of the kind now in progress at Tulane University 

 (Buchwald, 1956; Klopfer, 1956) will be required. From a 

 genetic standpoint, linkage and pleiotropism studies may be 

 helpful in an attempt to locate the chromosomal position of 

 the defective gene or genes and to detect the presence of such 

 gene effects in persons displaying no overt manifestation of 

 the disease process. In biochemical research, chromatographic 

 and electrophoretic methods may provide essential informa- 

 tion about the part played by amino acids and serum lipo- 

 proteins. 



Much additional genetic work is also needed in those dis- 

 orders in later life in which cerebrovascular changes are the 

 predominant feature. Obviously, arteriosclerotic symptoms 

 are developed much earlier and more severely by some persons 

 than others, and equally variable is the ability to withstand 

 cerebral damage (Adlersberg, Parets and Boas, 1949). 

 Clinically, it has also been established that atherosclerosis is a 

 disease in itself and not an ordinary concomitant of ageing. 

 In fact, it has been suggested by some investigators that 

 atherosclerosis may actually be two distinct diseases : the first 

 due to defects in cholesterol metabolism or circulatory 

 functions; the second resulting from a breakdown of the 

 structure of the elastic elements in the media of arteries, 

 accompanied by calcification. The increase in deposited 

 calcium has been shown to be associated with an increase in 

 some amino acids, which in turn may be related to the action 

 of elastase, a pancreatic hormone (Glass, 1955). 



In any case, it is particularly in the presence of a specific 

 disturbance in lipid metabolism (known as primary hyper- 

 cholesterolaemia) that a familial trend is found toward such 



