PMID- 38355687
OWN - NLM
STAT- MEDLINE
DCOM- 20240216
LR  - 20240218
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 14
IP  - 1
DP  - 2024 Feb 14
TI  - Potential Alzheimer's early biomarkers in a transgenic rat model and benefits of 
      diazoxide/dibenzoylmethane co-treatment on spatial memory and AD-pathology.
PG  - 3730
LID - 10.1038/s41598-024-54156-z [doi]
LID - 3730
AB  - Alzheimer's disease (AD) is the major form of dementia prevalent in older adults 
      and with a high incidence in females. Identification of early biomarkers is 
      essential for preventive intervention to delay its progression. Furthermore, due 
      to its multifactorial nature, a multi-target approach could be therapeutically 
      beneficial. Our studies included 4- (pre-pathology) and 11-month (mild-pathology) 
      TgF344-AD rats, a transgenic Alzheimer's model that exhibits age-dependent AD 
      progression. We identified two potential early biomarker genes for AD, early 
      growth response 2 (EGR2) and histone 1H2AA (HIST1H2AA), in the hippocampus of 
      4-month females. Out of 17,168 genes analyzed by RNA sequencing, expression of 
      these two genes was significantly altered in 4-month TgF344-AD rats compared to 
      wild-type littermates. We also evaluated co-treatment with diazoxide (DZ), a 
      potassium channel activator, and dibenzoylmethane (DIB), which inhibits eIF2alpha-P 
      activity, on TgF344-AD and wild-type rats. DZ/DIB-treatment mitigated spatial 
      memory deficits and buildup of hippocampal Abeta plaques and tau PHF in 11-month 
      TgF344-AD rats but had no effect on wild-type littermates. To our knowledge, this 
      preclinical study is the first to report EGR2 and HIST1H2AA as potential AD 
      biomarkers in females, and the benefits of DZ/DIB-treatment in AD. Evaluations 
      across multiple AD-related models is warranted to corroborate our findings.
CI  - (c) 2024. The Author(s).
FAU - Wallace, Charles H
AU  - Wallace CH
AD  - Department of Biological Sciences, Hunter College CUNY and Graduate Center, 695 
      Park Ave., New York, NY, USA.
FAU - Oliveros, Giovanni
AU  - Oliveros G
AD  - Department of Biological Sciences, Hunter College CUNY and Graduate Center, 695 
      Park Ave., New York, NY, USA.
FAU - Xie, Lei
AU  - Xie L
AD  - Department of Computer Sciences, Hunter College CUNY, New York, NY, USA.
FAU - Serrano, Peter
AU  - Serrano P
AD  - Department of Psychology, Hunter College CUNY, New York, NY, USA.
FAU - Rockwell, Patricia
AU  - Rockwell P
AD  - Department of Biological Sciences, Hunter College CUNY and Graduate Center, 695 
      Park Ave., New York, NY, USA.
FAU - Figueiredo-Pereira, Maria
AU  - Figueiredo-Pereira M
AD  - Department of Biological Sciences, Hunter College CUNY and Graduate Center, 695 
      Park Ave., New York, NY, USA. pereira@genectr.hunter.cuny.edu.
LA  - eng
GR  - R01 AG057555/AG/NIA NIH HHS/United States
GR  - R25 GM060665/GM/NIGMS NIH HHS/United States
GR  - R25GM060665/GF/NIH HHS/United States
PT  - Journal Article
DEP - 20240214
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - ANS7ME8OKC (dibenzoylmethane)
RN  - O5CB12L4FN (Diazoxide)
RN  - 0 (Biomarkers)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Chalcones)
SB  - IM
MH  - Female
MH  - Rats
MH  - Animals
MH  - *Alzheimer Disease/drug therapy/genetics/metabolism
MH  - Rats, Transgenic
MH  - Diazoxide/therapeutic use
MH  - Rats, Inbred F344
MH  - Spatial Memory
MH  - Biomarkers
MH  - Disease Models, Animal
MH  - Amyloid beta-Peptides
MH  - *Chalcones
PMC - PMC10867006
OTO - NOTNLM
OT  - Alzheimer's
OT  - Drug repurposing
OT  - EGR2
OT  - HIST1H2AA
OT  - Polypharmacology
OT  - Potassium channel activator
OT  - eIF2alpha activator
COIS- The authors declare no competing interests.
EDAT- 2024/02/15 00:42
MHDA- 2024/02/16 06:43
PMCR- 2024/02/14
CRDT- 2024/02/14 23:48
PHST- 2023/10/16 00:00 [received]
PHST- 2024/02/09 00:00 [accepted]
PHST- 2024/02/16 06:43 [medline]
PHST- 2024/02/15 00:42 [pubmed]
PHST- 2024/02/14 23:48 [entrez]
PHST- 2024/02/14 00:00 [pmc-release]
AID - 10.1038/s41598-024-54156-z [pii]
AID - 54156 [pii]
AID - 10.1038/s41598-024-54156-z [doi]
PST - epublish
SO  - Sci Rep. 2024 Feb 14;14(1):3730. doi: 10.1038/s41598-024-54156-z.