FILAMENTOUS AGGREGATES IN PICK'S DISEASE, PROGRESSIVE SUPRANUCLEAR PALSY, AND ALZHEIMER'S DISEASE SHARE ANTIGENIC DETERMINANTS WITH MICROTUBULE-ASSOCIATED PROTEIN, TAU

The Lancet ◽  
1986 ◽  
Vol 328 (8517) ◽  
pp. 1211 ◽  
Author(s):  
NancyJ. Pollock ◽  
SuzanneS. Mirra ◽  
LesterI. Binder ◽  
LawrenceA. Hansen ◽  
JohnG. Wood
Brain ◽  
2020 ◽  
Vol 143 (8) ◽  
pp. 2398-2405 ◽  
Author(s):  
Shinsuke Ishigaki ◽  
Yuichi Riku ◽  
Yusuke Fujioka ◽  
Kuniyuki Endo ◽  
Nobuyuki Iwade ◽  
...  

Abstract Fused in sarcoma (FUS) is genetically and clinicopathologically linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). We have previously reported that intranuclear interactions of FUS and splicing factor, proline- and glutamine-rich (SFPQ) contribute to neuronal homeostasis. Disruption of the FUS-SFPQ interaction leads to an increase in the ratio of 4-repeat tau (4R-tau)/3-repeat tau (3R-tau), which manifests in FTLD-like phenotypes in mice. Here, we examined FUS-SFPQ interactions in 142 autopsied individuals with FUS-related ALS/FTLD (ALS/FTLD-FUS), TDP-43-related ALS/FTLD (ALS/FTLD-TDP), progressive supranuclear palsy, corticobasal degeneration, Alzheimer’s disease, or Pick’s disease as well as controls. Immunofluorescent imaging showed impaired intranuclear co-localization of FUS and SFPQ in neurons of ALS/FTLD-FUS, ALS/FTLD-TDP, progressive supranuclear palsy and corticobasal degeneration cases, but not in Alzheimer’s disease or Pick’s disease cases. Immunoprecipitation analyses of FUS and SFPQ revealed reduced interactions between the two proteins in ALS/FTLD-TDP and progressive supranuclear palsy cases, but not in those with Alzheimer disease. Furthermore, the ratio of 4R/3R-tau was elevated in cases with ALS/FTLD-TDP and progressive supranuclear palsy, but was largely unaffected in cases with Alzheimer disease. We concluded that impaired interactions between intranuclear FUS and SFPQ and the subsequent increase in the ratio of 4R/3R-tau constitute a common pathogenesis pathway in FTLD spectrum diseases.


1943 ◽  
Vol 89 (374) ◽  
pp. 1-20 ◽  
Author(s):  
E. Stengel

Many problems concerning Alzheimer's disease and Pick's disease are still awaiting clarification. In this country Henderson was the first to draw attention to the considerable importance of Alzheimer's disease in clinical psychiatry. Valuable work has been contributed by various writers in recent years (Grunthal, 1936; Critchley, 1929, 1930, 1931, 1938; Schottky, 1932; Thorpe, 1932; Rothschild, 1934; Malamud, Lowenberg and co-workers, 1929; Mayer-Gross, 1938; Kasanin and Crank, 1933; Jervis and Soltz, 1936; McMenemy, a.o., 1939). While Pick's disease has retained its position as a clinical entity based mainly on the characteristic anatomical picture, the position of Alzheimer's disease in the system of psychiatry has become more complicated; for instance atypical cases have been described presenting the anatomical characters of Alzheimer's disease, though not fitting into the original clinical conception of that disease. Lowenberg and his co-workers (1929) are inclined to regard Alzheimer's disease as a syndrome rather than a clinical entity. Many contributors have directed their main interest to the pathological changes. The knowledge of the symptomatology of those conditions is still incomplete. Further intensive study may enable us not only to base the diagnosis and differential diagnosis of Alzheimer's disease and Pick's disease on more solid clinical knowledge than hitherto, but also to recognize the early stages of those diseases before advancing cerebral degeneration effaces their characteristic clinical features. Unfortunately, most of the cases come under the observation of the psychiatrist only in the later stages of their illness, and it seems that the comparatively small proportion of the mental hospital population they represent does not reflect the incidence of those diseases. It is very likely that many patients die from intercurrent illnesses before their mental condition is recognized or sufficiently advanced to make admission to a mental hospital necessary. The differential diagnosis of those conditions offers considerable difficulties which often may prove insuperable. Alzheimer's disease and Pick's disease have to be distinguished not only from each other but from conditions of vascular origin, from senile dementia and various atypical conditions which occur at the same age period during which Alzheimer's disease and Pick's disease usually develop. Only careful collection and analysis of clinical observations and their scrutiny by pathological investigations can increase our still limited knowledge in this important field of psychiatry.


1983 ◽  
Vol 62 (1-3) ◽  
pp. 211-217 ◽  
Author(s):  
P.L. Wood ◽  
P. Etienne ◽  
S. Lal ◽  
N.P.V. Nair ◽  
M.H. Finlayson ◽  
...  

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