Distribution of SLC10A4, a synaptic vesicle protein in the human brain, and the association of this protein with Alzheimer's disease-related neuronal degeneration.
Member 4 of the sodium/bile acid co-transporter family of proteins (SLC10A4) was discovered as a synaptic vesicle protein. The distribution of Slc10a4 protein in the brain has only so far been assessed in adult rats. Here, we assessed the regional distribution of SLC10A4 in aged human brain by immunohistochemistry. The protein was ubiquitously expressed, particularly in the cholinergic and monoaminergic neurons and in the lateral geniculate body. The protein expression was not influenced by the postmortem delay or fixation time. Synaptic alterations are reported to be seen in Alzheimer's disease (AD) and the suggested function of SLC10A4 as a vesicular transporter for cholinergic neurotransmitters proposes a link between this protein and AD. With increased severity of AD-related pathology, depletion of SLC10A4 expression was noted in the transentorhinal cortex. Intriguingly, in the most severely affected cases (Braak V), two patterns were noted, i.e., those with severe depletion of SLC10A4 and those with numerous neurons displaying SLC10A4. In conclusion, assessment of the expression of SLC10A4 by means of immunohistochemistry is feasible. The observed depletion of SLC10A4 with increase in the severity of AD-related neuronal degeneration is interesting and the observation that some subjects in Braak V displayed none and some displayed numerous SLC10A4 immunoreactive neurons is intriguing. Assessment of the SLC10A4 protein in neurodegenerative diseases or diseases affecting lateral geniculate body should be carried out to investigate whether alterations in the expression of SLC10A4 in synaptic vesicles might be used as a marker of transmitter deficits (cholinergic, monoaminorgic) or other synaptic pathology.
Department of Pathology and Cytology, Uppsala University Hospital, Uppsala, Sweden.
Svetlana N
SN
Popova
Irina
I
Alafuzoff
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D029363:Organic Anion Transporters, Sodium-Dependent / Q000032:analysis / Q000096:biosynthesis*; D011485:Protein Binding; D012720:Severity of Illness Index; D027981:Symporters / Q000032:analysis / Q000096:biosynthesis*; D013572:Synaptic Vesicles / Q000737:chemistry / Q000378:metabolism*
D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter