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. 2017 Jul 19;95(2):297–308.e6. doi: 10.1016/j.neuron.2017.05.037

Figure 5.

Figure 5

Prevalence of AD in ALS/FTLD Patients Is Significantly Lower than in Healthy Controls

(A) Prevalence of AD in ALS patients compared to expected prevalence in a normal age-matched population. ALS cohort was divided into two sub-groups according to their age at the time of AD screening: 65–74 and ≥75 years. The expected prevalence of AD in these age groups is 3% and 17%, respectively. AD prevalence is 4.7% in ALS patients aged 65–74 years but increases to only 7.1% in those ≥75 years.

(B) MiniMental State Examination (MMSE) scores reported from ALS patients with or without AD, indicate a mild cognitive impairment in ALS patients above 75, despite no AD.

(C) Representative images of beta-amyloid load in Control, ALS, FTLD, and AD biopsies in 65–74 and ≥75 years cases.

(D) Amyloid burden quantified according to the Thal Aβ phase (TAP) scoring system, in 65–74 and ≥75 years controls, ALS, FTLD, and AD cases indicates decreased Aβ in ALS and FTLD cases ≥75 years (mean ± SEM, Control n = 40, ALS n = 35, FTLD n = 25, AD n = 62, ∗p < 0.05, ∗∗∗∗p < 0.0001, by one-way ANOVA of unpaired t test, followed by Holm-Sidak’s multiple comparisons test).

(E and F) Representative micrographs for immunostaining against CD68 in cortical section of healthy control, and ALS cases negative and positive for TDP-43 pathology, respectively (E). Relative quantification of CD68 burden in ALS patients with and without TDP-43 pathology indicates increased burden in ALS patients with TDP-43 pathology (F) (mean ± SEM, Control n = 6; ∗p < 0.05, ALS TDP-43 negative (n = 11) versus ALS TDP-43 positive (n = 16), by using two-tailed unpaired t test); scale bar: 50 μm.

(G) Representative confocal z stack and orthogonal projections of microglial cells positive for Iba1 and pTDP-43 markers, in human post-mortem cortical sections of MND cases; scale bar: 20 μm; scale bar for the orthogonal projection: 40 μm.