PMID- 25933387
OWN - NLM
STAT- MEDLINE
DCOM- 20150727
LR  - 20220316
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Linking)
VI  - 74
IP  - 6
DP  - 2015 Jun
TI  - TDP-43 Pathology Progression Along the Olfactory Pathway as a Possible Substrate 
      for Olfactory Impairment in Amyotrophic Lateral Sclerosis.
PG  - 547-56
LID - 10.1097/NEN.0000000000000198 [doi]
AB  - Odor impairment and its relationship with TAR DNA-binding protein 43 (TDP-43) 
      pathology in patients with amyotrophic lateral sclerosis (ALS) have not been 
      fully elucidated. We performed the odor stick identification test for Japanese 
      (OSIT-J) in 18 ALS patients and in 18 controls. The score was significantly 
      decreased (6.6 +/- 2.7) in the patients versus the controls (9.2 +/- 2.4) (U = 77.0, 
      p = 0.007). This decrement of the OSIT-J score paralleled the cognitive decline. 
      We then studied samples from a series of 42 postmortem ALS cases. Quantitative 
      analyses demonstrated that TDP-43-positive inclusions were most frequent in the 
      hippocampus and least abundant in the olfactory bulb and were of intermediate 
      density in the primary olfactory cortex. This centrifugal gradient suggests that 
      TDP-43 pathology starts in the hippocampus, spreads into the primary olfactory 
      center, and finally reaches the olfactory bulb. TDP-43, tau, and alpha-synuclein 
      accumulations appeared to be independent. These observations suggest that 
      impaired odor discrimination in ALS patients may be related to TDP-43-positive 
      lesions affecting predominantly secondary olfactory centers (especially the 
      hippocampus) in contrast to decreased odor sensitivity in Parkinson disease in 
      which alpha-synuclein pathology mainly involves the peripheral region (i.e., 
      olfactory bulb). We suggest that detectable odor impairments in ALS patients are 
      useful for predicting the presence of TDP-43 pathology in the extramotor system.
FAU - Takeda, Takahiro
AU  - Takeda T
AD  - From the Department of Neurology, Tokyo Women's Medical University (TT, MI, SU); 
      Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical 
      Science (TT, TU); Department of Neurology, Tokyo Women's Medical University 
      Yachiyo Medical Center, Tokyo, Japan (TO); and Raymond Escourolle Laboratory of 
      Neuropathology, Universite Pierre et Marie Curie, Assistance Publique-Hopitaux de 
      Paris, La Salpetriere Hospital, Paris, France (TT, DS, CD).
FAU - Iijima, Mutsumi
AU  - Iijima M
FAU - Uchihara, Toshiki
AU  - Uchihara T
FAU - Ohashi, Takashi
AU  - Ohashi T
FAU - Seilhean, Danielle
AU  - Seilhean D
FAU - Duyckaerts, Charles
AU  - Duyckaerts C
FAU - Uchiyama, Shinichiro
AU  - Uchiyama S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (TARDBP protein, human)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Amyotrophic Lateral Sclerosis/*complications
MH  - Analysis of Variance
MH  - Cognition Disorders/etiology
MH  - DNA-Binding Proteins/*metabolism
MH  - Disease Progression
MH  - Female
MH  - Hippocampus/*metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Olfaction Disorders/*etiology/*pathology
MH  - Olfactory Cortex/*metabolism
MH  - Statistics, Nonparametric
EDAT- 2015/05/02 06:00
MHDA- 2015/07/28 06:00
CRDT- 2015/05/02 06:00
PHST- 2015/05/02 06:00 [entrez]
PHST- 2015/05/02 06:00 [pubmed]
PHST- 2015/07/28 06:00 [medline]
AID - 10.1097/NEN.0000000000000198 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2015 Jun;74(6):547-56. doi: 
      10.1097/NEN.0000000000000198.