TY  - CHAP
M1  - Book, Section
TI  - Alzheimer Disease and the Frontotemporal Dementias: Diseases with Cerebral Deposition of Fibrillar Proteins
A1  - George-Hyslop, P. H.
A1  - Farrer, L. A.
A1  - Goedert, M.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
PY  - 2019
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Alzheimer  disease  (AD),  Lewy  body  variant  of  Alzheimer  disease  (LBV),  and  the  frontotemporal  dementias  (FTD)  are  a  class  of  adult-onset  neurodegenerative  dementias  characterized  by  the  intracellular  and/or  extracellular  accumulation  of  proteins  which  assemble  into  β-pleated  sheet  fibrils.Missense  mutations  in  the  β-amyloid  precursor  protein  (βAPP)  gene  on  chromosome  21,  in  the  presenilin  1  (PS1)  gene  on  chromosome  14,  and  the  presenilin  2  (PS2)  on  chromosome  1,  are  associated  with  early-onset  forms  of  familial  Alzheimer  disease.  Mutations  in  these  genes  result  in  altered  processing  of  βAPP  and  the  relative  overproduction  of  either  all  forms  of  the  β-amyloid  peptide  or  specific  overproduction  of  isoforms  ending  at  residue  42.The  ∈4  (Cys112Arg)  variant  of  apolipoprotein  E  (APOE)  is  associated  in  a  dose-dependent  fashion  with  increased  risk  for  late-onset  Alzheimer  disease  (after  age  55)  and  with  Lewy  body  variant  of  Alzheimer  disease.  The  inheritance  of  one  or  more  APOE  ∈4  alleles  is  not  deterministic  for  AD,  and  the  mechanism  by  which  inheritance  of  one  or  more  ∈4  alleles  causes  AD  is  unclear.Allelic  association  studies  have  identified  several  putative  candidate  genes  in  which  nucleotide  sequence  variants  have  been  associated  with  AD.  These  studies  have  received  only  partial  replication,  and  the  true  role  of  these  candidate  genes  in  AD  remains  unclear.Hyperphosphorylated  forms  of  the  microtubule-associated  protein  Tau  are  consistent  neuropathologic  features  of  AD,  LDV,  and  FTD.  Coding  region  and  splice-site  mutations  in  the  Tau  gene  on  chromosome  17  are  associated  with  a  subtype  of  frontotemporal  dementia  (FTDP-17).  These  mutations  probably  affect  filament  assembly  by  several  different  mechanisms  including  alterations  in  the  sequence  of  microtubule  binding  sites  and  alterations  in  the  relative  abundance  of  longer  (4  repeat)  isoforms  of  Tau  relative  to  shorter  (3  repeat)  isoforms.The  currently  identified  genes  associated  with  inherited  risk  for  these  diseases  represent  approximately  half  of  the  probable  genetic  factors  causing  these  diseases.  As  the  remaining  susceptibility  genes  are  identified,  they  will  likely  contribute  to  a  more  complete  understanding  of  the  pathogenesis  of  these  disorders.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/17
UR  - ommbid.mhmedical.com/content.aspx?aid=1181480064
ER  -