Accelerated Tau deposition in the brains of individuals infected with human immunodeficiency virus-1 before and after the advent of highly active anti-retroviral therapy.
This study aims to investigate the influence of human immunodeficiency virus (HIV) infection on the neurodegenerative processes normally associated with ageing. We have looked for evidence of beta amyloid and hyperphosphorylated Tau deposition in HIV-infected subjects before and after the advent of highly active anti-retroviral therapy (HAART). In addition we have looked for evidence of axonal damage. We have compared these HIV-positive cases with age-matched controls and with older non-demented controls. We find no evidence of significant premature beta amyloid deposition in HIV-infected cases; however, we do observe elevated levels of hyperphosphorylated Tau in the hippocampus of many HIV-infected subjects, compared with age-matched controls. The greatest levels of hyperphosphorylated Tau are noted in HAART-treated subjects. Axonal damage marked by expression of beta amyloid pre-cursor protein (BAPP) was highly variable in all groups including control subjects. We surmise that HIV infection and/or the use of anti-retroviral therapy may predispose to accelerated neuroageing in the form of hyperphosphorylated Tau deposition in the hippocampus. Within the age groups studied these significant neuropathological changes remained subclinical and were not yet associated with cognitive impairment.
Anthony
Iain C
IC
Department of Pathology (Neuropathology), University of Edinburgh, Western General Hospital, Alexander Donald Building, EH4 2XU, Edinburgh, UK.
Ramage
Stephen N
SN
Carnie
Frances W
FW
Simmonds
Peter
P
Bell
Jeanne E
JE
D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active; D001369:Axons / Q000473:pathology; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry / Q000502:physiology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D015497:HIV-1; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology; D016612:Paraffin Embedding; D011149:Pons / Q000473:pathology; D014015:Tissue Banks; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016875:tau Proteins