Table 1 Epidemiological studies of p-tau and t-tau in HAND

Green et al. [35]

Cerebrospinal fluid tau concentrations in HIV infected patients with suspected neurological Disease

1) Mean age: 37 yr. with acute neurological episodes

ELISA (INNOTEST, Fujirebio Europe/Innogenetics, Ghent, Belgium)

t-tau: 75-316

1) CSF tau not elevated in 82% of patients, regardless of clinical diagnoses.

2) N = 76 (24-HAD, 10 lymphoma, 20 cerebral infarctions, 22 miscellaneous conditions such as headache)

2) Elevated CSF tau was associated with poor outcome as 6 of 8 patients who died within 4 weeks of lumbar puncture.

3) cART not accounted for

Brew et al. [37]

CSF amyloid beta42 and tau levels correlate with AIDS dementia complex

1) Mean age: 43 years

ELISA (INNOTEST, Fujirebio Europe/Innogenetics, Ghent, Belgium)

Upper limits not reported /lower limits: t-tau: 75, p-tau:16

1) HAND subjects had significantly increased t-tau and p-tau at residue 181 (p-Tau181) at concentrations similar to patients with AD

2) N = 101 HIV positive subjects with or without ADC with 20 moderate to severe AD subjects as positive control

2) p-tau levels significantly increased in all of the ADC stages compared with the negative controls and the AD patients.

3) cART not accounted for.

Anthony et al. [54]

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

1) Mean age: 40 for HIV- control group and HIV positive cases, 70 for HIV negative control group and 40 for HIV negative control group B

Immunohistocytochemistry (TSA was used in instances where avidin-biotin complex ABC was not sensitive enough, with DBA for visualization.)

NA: AT8 antibody used on paraffin sections

1) Higher levels of p-tau in HIV infectedsubjects vs. aged matched controls.

2) N = 34

2) Greatest levels of p-tau were noted in cART-treated subjects.

3) Nine cART treated subjects with excellent compliance for at least 18 months with pre-symptomatic HIV or AIDS and 20 pre-cART HIV subjects

3) Increased t- tau in hippocampal region of pre-cART HIV-infected groups compared to HIV-negative age-matched controls

Clifford et al. [39]

CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease

1) Mean age: normal cognition control group (50 years), HIV + normal cognition (43 years), HAND subjects (48 years), mild AD subjects (74 years)

ELISA, (INNOTEST, Fujirebio Europe/Innogenetics, Ghent, Belgium)

Not reported

HIV-positive subjects with HAND did not have CSF t-tau and p-tau181 characteristic of AD

2) N = 188 (50 control, 68 AD subjects, 21 Neuro-normal HIV positive subjects and 49 HAND subjects.

3) HIV patients were not treated with cART.

Patrick et al. [55]

Increased CDK5 expression in HIV encephalitis contributes to neurodegeneration via tau phosphorylation and is reversed with Roscovitine

1) Mean age: HIVE patients - 43.13 years, Non HIVE subjects (48.38 years )

Immunohistochemistry

N/A:AT8 and PHF-antibody detection on post-mortem brain

Elevated diffuse nonfibrriliar p-tau in HIVE group and HIV gp120 tg mice.

2) N = 16: 8 HIVE subjects, 8 HIV positive without HIVE

(TSA was used in instances where avidin-biotin complex ABC was not sensitive enough, with DBA for visualization.)

3) cART not accounted for

Steinbrink et. al. [56]

Cognitive impairment in HIV infection is associated with MRI and CSF pattern of neurodegeneration

1) Mean age: 45 ± 10 years

ELISA (INNOTEST, Fujirebio Europe/Innogenetics, Ghent, Belgium)

Not reported

1) Significant correlation between HAND and t-tau but not p-tau

2) N = 94. All patients were HIV positive with varying levels of neuropsychological performance,

2) HAND severity correlated significantly with the t- tau level in CSF but not p-tau levels

3) 68% cART treated

Smith et al. [57]

Brain viral burden, neuroinflammation and neurodegeneration in HAART-treated HIV positive injecting drug users

1) Mean age: 45.8 years for HIV+, 42.2 years for HIV-

Immunohistochemistry

NA: AT8 on post-mortem brain

1) IDU had more t- tau vs. non-DU

2.) N = 20 :10 HIV + (6 IDU, 4 non-IDU),10 HIV (6 IDU, 4 non-IDU)

(TSA was used in instances where avidin-biotin complex ABC was not sensitive enough, with DBA for visualization.)

2) HIV + subjects had more t-tau than HIV -, but these differences did not achieve statistical significance.

3) HIV + patients treated with cART for up to 7.9 years