Tyrosine hydroxylase and norepinephrine transporter mRNA expression in the locus coeruleus in Alzheimer's disease.
Despite the loss of locus coeruleus (LC) noradrenergic neurons in Alzheimer's disease (AD), cerebrospinal fluid norepinephrine (NE) levels are normal or increased in AD. This paradox suggests compensatory upregulation of NE synthetic capacity or downregulation of the NE transporter (NET) in the remaining LC neurons. LC tyrosine hydroxylase (TH) mRNA expression in the LC was measured in AD subjects (n=5) and in age and gender comparable non-demented subjects (n=6). When AD subjects were divided into those still ambulatory prior to death (CDR 3/4) and those in a prolonged 'vegetative' state prior to death (CDR 5), differences among groups became apparent at specific levels of the LC. In CDR 3/4 AD subjects there was increased TH mRNA expression per neuron compared to non-demented subjects in the caudal half of the LC. However, expression of NET mRNA in the same subjects was not significantly different at any level of the LC. These preliminary results suggest an upregulation of NE biosynthetic capacity in at least some LC neurons in AD prior to the very late stage of the disease.
Szot
P
P
Northwest Network Mental Illness Research, Education and Clinical Center, Veterans Administration Puget Sound Health Care System, Seattle, WA 98108, USA. szot@u.washington.edu
Leverenz
J B
JB
Peskind
E R
ER
Kiyasu
E
E
Rohde
K
K
Miller
M A
MA
Raskind
M A
MA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D008125:Locus Coeruleus / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D027981:Symporters; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D002352:Carrier Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; C493227:SLC6A2 protein, human; D027981:Symporters; D014446:Tyrosine 3-Monooxygenase