PMID- 28462473
OWN - NLM
STAT- MEDLINE
DCOM- 20180518
LR  - 20181113
IS  - 1550-7416 (Electronic)
IS  - 1550-7416 (Linking)
VI  - 19
IP  - 4
DP  - 2017 Jul
TI  - Neurovascular Alterations in Alzheimer's Disease: Transporter Expression Profiles 
      and CNS Drug Access.
PG  - 940-956
LID - 10.1208/s12248-017-0077-5 [doi]
AB  - Despite a century of steady and incremental progress toward understanding the 
      underlying biochemical mechanisms, Alzheimer's disease (AD) remains a complicated 
      and enigmatic disease, and greater insight will be necessary before substantive 
      clinical success is realised. Over the last decade in particular, a large body of 
      work has highlighted the cerebral microvasculature as an anatomical region with 
      an increasingly apparent role in the pathogenesis of AD. The causative interplay 
      and temporal cascade that manifest between the brain vasculature and the wider 
      disease progression of AD are not yet fully understood, and further inquiry is 
      required to properly characterise these relationships. The purpose of this review 
      is to highlight the recent advancements in research implicating neurovascular 
      factors in AD, at both the molecular and anatomical levels. We begin with a brief 
      introduction of the biochemical and genetic aspects of AD, before reviewing the 
      essential concepts of the blood-brain barrier (BBB) and the neurovascular unit 
      (NVU). In detail, we then examine the evidence demonstrating involvement of BBB 
      dysfunction in AD pathogenesis, highlighting the importance of neurovascular 
      components in AD. Lastly, we include within this review research that focuses on 
      how altered properties of the BBB in AD impact upon CNS exposure of therapeutic 
      agents and the potential clinical impact that this may have on people with this 
      disease.
FAU - McInerney, Mitchell P
AU  - McInerney MP
AD  - Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical 
      Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.
FAU - Short, Jennifer L
AU  - Short JL
AD  - Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash 
      University, Parkville, 3052, VIC, Australia.
FAU - Nicolazzo, Joseph A
AU  - Nicolazzo JA
AD  - Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical 
      Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia. 
      joseph.nicolazzo@monash.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20170501
PL  - United States
TA  - AAPS J
JT  - The AAPS journal
JID - 101223209
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Low Density Lipoprotein Receptor-Related Protein-1)
RN  - 0 (Membrane Transport Proteins)
SB  - IM
MH  - Alzheimer Disease/*metabolism/pathology
MH  - Amyloid beta-Peptides/metabolism
MH  - Blood-Brain Barrier
MH  - Central Nervous System/*metabolism
MH  - Humans
MH  - Low Density Lipoprotein Receptor-Related Protein-1/metabolism
MH  - Membrane Transport Proteins/*metabolism
MH  - Risk Factors
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - CNS drug delivery
OT  - blood-brain barrier
OT  - neurovascular unit
OT  - transporters
EDAT- 2017/05/04 06:00
MHDA- 2018/05/19 06:00
CRDT- 2017/05/03 06:00
PHST- 2017/01/26 00:00 [received]
PHST- 2017/03/15 00:00 [accepted]
PHST- 2017/05/04 06:00 [pubmed]
PHST- 2018/05/19 06:00 [medline]
PHST- 2017/05/03 06:00 [entrez]
AID - 10.1208/s12248-017-0077-5 [pii]
AID - 10.1208/s12248-017-0077-5 [doi]
PST - ppublish
SO  - AAPS J. 2017 Jul;19(4):940-956. doi: 10.1208/s12248-017-0077-5. Epub 2017 May 1.