PMID- 10339611
OWN - NLM
STAT- MEDLINE
DCOM- 19990624
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 11
DP  - 1999 May 25
TI  - Agrin in Alzheimer's disease: altered solubility and abnormal distribution within
      microvasculature and brain parenchyma.
PG  - 6468-72
AB  - Agrin is a heparan sulfate proteoglycan that is widely expressed in neurons and
      microvascular basal lamina in the rodent and avian central nervous system. Agrin 
      induces the differentiation of nerve-muscle synapses, but its function in either 
      normal or diseased brains is not known. Alzheimer's disease (AD) is characterized
      by loss of synapses, changes in microvascular architecture, and formation of
      neurofibrillary tangles and senile plaques. Here we have asked whether AD causes 
      changes in the distribution and biochemical properties of agrin. Immunostaining
      of normal, aged human central nervous system revealed that agrin is expressed in 
      neurons in multiple brain areas. Robust agrin immunoreactivity was observed
      uniformly in the microvascular basal lamina. In AD brains, agrin is highly
      concentrated in both diffuse and neuritic plaques as well as neurofibrillary
      tangles; neuronal expression of agrin also was observed. Furthermore, patients
      with AD had microvascular alterations characterized by thinning and fragmentation
      of the basal lamina. Detergent extraction and Western blotting showed that
      virtually all the agrin in normal brain is soluble in 1% SDS. In contrast, a
      large fraction of the agrin in AD brains is insoluble under these conditions,
      suggesting that it is tightly associated with beta-amyloid. Together, these data 
      indicate that the agrin abnormalities observed in AD are closely linked to
      beta-amyloid deposition. These observations suggest that altered agrin expression
      in the microvasculature and the brain parenchyma contribute to the pathogenesis
      of AD.
FAU - Donahue, J E
AU  - Donahue JE
AD  - Department of Pathology (Neuropathology Division), Brown University, Rhode Island
      Hospital, 593 Eddy Street, Providence, RI 02903, USA.
FAU - Berzin, T M
AU  - Berzin TM
FAU - Rafii, M S
AU  - Rafii MS
FAU - Glass, D J
AU  - Glass DJ
FAU - Yancopoulos, G D
AU  - Yancopoulos GD
FAU - Fallon, J R
AU  - Fallon JR
FAU - Stopa, E G
AU  - Stopa EG
LA  - eng
GR  - R01 HD023924/HD/NICHD NIH HHS/United States
GR  - AG10682/AG/NIA NIH HHS/United States
GR  - HD23924/HD/NICHD NIH HHS/United States
GR  - MH53571/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Agrin)
SB  - IM
MH  - Aged
MH  - Agrin/chemistry/*metabolism
MH  - Alzheimer Disease/*pathology/physiopathology
MH  - Brain/*blood supply/*metabolism/pathology
MH  - *Cerebrovascular Circulation
MH  - Female
MH  - Humans
MH  - Male
MH  - Microcirculation/metabolism/*pathology
MH  - Neurons/*metabolism/pathology
MH  - Reference Values
MH  - Solubility
PMC - PMC26905
EDAT- 1999/05/26 00:00
MHDA- 1999/05/26 00:01
CRDT- 1999/05/26 00:00
PHST- 1999/05/26 00:00 [pubmed]
PHST- 1999/05/26 00:01 [medline]
PHST- 1999/05/26 00:00 [entrez]
AID - 10.1073/pnas.96.11.6468 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 May 25;96(11):6468-72. doi:
      10.1073/pnas.96.11.6468.