Table 2.
Summary of Neuropathological, Biochemical and Functional Data in Hereditary Pick Disease
|
MAPT mutation |
Lobar atrophy; [brain wt.] |
Tau isoform in TB |
Western blot (kDa) |
EM Filament width (nm); (half period) |
Pick bodies | Cell type specificity |
Microtubule assembly | Tau filament assembly | ||
|---|---|---|---|---|---|---|---|---|---|---|
| 12E8 | Other stains | Distribution | ||||||||
| p.K257T (38) |
Severe temporal; moderate frontal; hippocampus; [1120 g] |
3R>4R (TB) |
60, 64 (minor 68, 72) |
14 SF & twisted ribbons (>130 nm) | neg | Palmgren (pos) | Hp: dentate gyrus & pyramidal; Ctx: temporal | neuronal>glial few A |
reduced (95% for 3R; 85% for 4R) (38), reduced (70% for 4R) (39) | increased for 3R, but not for 4R |
| p.G272V (11) |
Severe frontal & temporal; hippocampus; amygdala; [880 g] |
3R>4R (TB) |
60, 64 (frontal also 68) |
20; twisted ribbons (110 nm) | neg | Gallyas (pos); 3R NFT 4R (IM) |
Hp: dentate gyrus & pyramidal; Ctx: frontal | neuronal>glial few A & O |
reduced (70% for 3R; 60% for 4R) (40) | increased for 4R>3R (41) |
| p.ΔK280 (18) |
Severe frontal & temporal; hippocampus; amygdala; [870 g] |
3R>4R front, 3R temp (TB) |
60, 64 | 7 – 8; PHF (95 nm) | neg | Gallyas (neg); 3R (IM) |
Hp: dentate gyrus & pyramidal; Ctx: frontal & temporal | neuronal>glial many A & few O |
reduced for 3R and 4R (42) | increased for 4R (41) |
| p.S320F (19) |
Severe anterior temporal; [1200 g] |
3R=4R (TB) |
60, 64 | 6–8 SF & twisted ribbons (110–160 nm) | neg | Bodian (neg) | Hp: dentate gyrus & pyramidal; Ctx: frontal, temporal, & parietal | neuronal>glial few O |
reduced (90 – 95% for 3R and 4R) | N/A |
| p.Q336R (16) |
Severe temporal; moderate frontal; hippocampus; amygdala; [1100 g] |
3R & 4R (TB) |
N/A | SF & twisted ribbons | mostly neg | 3R>4R (IM) (43) | Hp: dentate gyrus & pyramidal; Ctx: frontal & temporal | neuronal>glial rare A & O | increased (40% for 3R and 4R) | increased (3–4 fold for 3R>4R) |
| p.Q336H | Severe frontal; hippocampus; amygdala; [1120 g] |
N/A | 60, 64 | 10–15 SF & twisted ribbons (100 nm) | mostly neg | Bielschowsky (pos); Gallyas (neg); 3R>4R (IM) | Hp: dentate gyrus & pyramidal; Ctx: frontal & temporal | neuronal>glial few A & O | increased (4R>3R) | increased (13.8 fold; 3R>4R) |
| p.K369I (20) |
Severe temporal; moderate frontal; hippocampus; amygdala; [880 g] |
3R & 4R (TB) (20) |
60, 64, 68 | 28 twisted ribbons (130 nm) few PHF | neg | Bielschowsky (pos): Gallyas (neg); 3R (IM) (43) | Hp: dentate gyrus & pyramidal; Ctx: frontal, temporal, parietal, insular | neuronal>glial rare A & rare O | reduced (90% for 3R and 70% for 4R) | no effect on 3R or 4R |
Wt, weight; g, gram; 4R, four repeat tau isoform; 3R, three repeat tau isoform; IM, tau immunostaining; TB, Tau biochemistry (mostly Western blotting of dephosphorylated sarkosyl-insoluble tau); NFT, neurofibrillary tangles; PB, Pick bodies; PHF, Paired helical filaments; Hp, hippocampus; Ctx, neocortex; A, astrocytes; O, oligodendrocytes; pos, positive; neg, negative; SF, straight filaments; front, frontal cortex; temp, temporal cortex.