RT Book, Section
A1 Prusiner, Stanley B.
A1 Geschwind, Michael
A2 Loscalzo, Joseph
A2 Fauci, Anthony
A2 Kasper, Dennis
A2 Hauser, Stephen
A2 Longo, Dan
A2 Jameson, J. Larry
SR Print(0)
ID 1190506018
T1 Prion Diseases
T2 Harrison's Principles of Internal Medicine, 21e
YR 2022
FD 2022
PB McGraw-Hill Education
PP New York, NY
SN 9781264268504
LK accessmedicine.mhmedical.com/content.aspx?aid=1190506018
RD 2024/04/23
AB Prions  are  proteins  that  adopt  alternative  conformations,  which  become  self-propagating.  Some  prions  cause  degeneration  of  the  central  nervous  system  (CNS).  Once  relegated  to  causing  a  group  of  rare  CNS  disorders,  such  as  Creutzfeldt-Jakob  disease  (CJD),  increasing  evidence  argues  that  prions  cause  more  common  neurodegenerative  diseases  (NDs)  including  Alzheimer’s  disease  (AD)  and  Parkinson’s  disease  (PD).  While  CJD  is  caused  by  the  accumulation  of  PrPSc  prions,  recent  investigations  demonstrate  unequivocally  that  α-synuclein  prions  cause  multiple  system  atrophy  (MSA)  (Chap.  440).  Infectious  MSA  prions  have  been  recovered  from  human  brain  samples  stored  in  formalin  for  up  to  20  years.  Similar  resistance  to  formalin  was  demonstrated  for  brain  samples  from  sheep  with  scrapie.  Increasingly,  studies  show  that  Aβ  and  tau  prions  together  cause  AD,  α-synuclein  prions  cause  both  PD  and  MSA,  and  tau  prions  alone  cause  frontotemporal  lobar  degeneration  (FTLD).  In  this  chapter,  we  confine  our  discussion  to  CJD,  which  typically  presents  with  a  rapidly  progressive  dementia  as  well  as  motor  and  behavioral  abnormalities.  The  illness  is  relentlessly  progressive  and  generally  causes  death  within  7  months  of  onset.  Most  patients  with  CJD  are  between  50  and  75  years  of  age;  however,  patients  as  young  as  12  and  as  old  as  96  have  been  recorded.  The  role  of  prions  in  the  pathogenesis  of  NDs  is  reviewed  in  Chap.  424.